5 Deadly Diseases for Your Campaign in D&D 5e

The world of Dungeons & Dragons is filled with dangers, but the greatest danger of all might be lurking within your players, waiting to take hold. Diseases are a great way to create mystery, tension and intrigue in your D&D campaign!

What are the some diseases in D&D 5e?

  • Sewer Plague
  • Eye Rot
  • Cackle Fever
  • Madness
  • Homebrewed Diseases (Anything you can come up with!)

Each of these has unique symptoms, cures and effects. Knowing which disease to use at what part in your campaign can increase drama and emotion. And if your players ever “outgrow” these, you can always create your own diseases.

Sewer Plague

Symptoms & Effects

Want to travel the city quickly and stealthy? The sewers are a great option, but, not always the safest. Diseased rats and other creatures live in the sewers of cities, carrying deadly diseases.

After being bitten by a creature infected with Sewer Plague, the player must make a DC 13 Constitution Saving Throw. On a failed save, the player is infected with Sewer Plague, but does not experience symptoms until 14 days later.

Players infected with Sewer Plague suffer 1 point of exhaustion, receive half healing from expending hit dice and receive no healing from a long rest.

After each long rest, infected players must make a DC 11 Constitution Saving Throw, on a failed save player gains one level of exhaustion, a successful save reduces the player’s exhaustion level by one. If the exhaustion level is reduced to 0, the player recovers from the disease.

Cures for Sewer Plague

Sewer Plague is cured when the player’s exhaustion level is reduced to 0. Exhaustion levels are only reduced after players make a successful Constitution Saving Throw (DC 11) after each long rest.

This disease can also be cured by a Lesser Restoration spell or by the Paladin ability Lay on of Hands. The spells Healing Word and Cure Wounds have no effect on this disease.

Eye Rot

Symptoms & Effects

Adventurers rely on their sight to spot potential danger and attack enemies. Found in swamps and bogs, Sight Rot is an extremely painful disease. The most prominent symptom of Sight Rot is bleeding from the eyes which eventually causes the victim to go blind.

A player can become infected with sight rot if they ingest contaminated water, intentionally or unintentionally (such as being dragged under water during combat).

When a player drinks water contaminated with Sight Rot, he/she must make a DC 15 Constitution Save to avoid becoming infected. If infected, the next day the player’s eyesight begins to deteriorate, giving them a -1 penalty on all attack rolls and any ability check that relies on sight.

With every long rest after the symptoms first appear, the disease worsens (feel free to provide descriptions of the blood in the eyes and the pain it causes for the characters to role-play). After a long rest, the penalty increases by -1, until it reaches -5 then the player suffers from the Blinded effect.

Cures for Eye Rot

If the players have proficiency in Nature or Medicine, they can roll to see if they know the disease and the cure (DC 13 recommended). On a successful roll, the players know the effects of Sight Rot can be negated with an ointment created from a rare flower, called Sight Bright. Sight Bright is found in some swamps and I recommend a DC 15 Survival or Nature Check to find it (once per day). A player with proficiency in Herbalism can turn 1 flower into 1 dose of ointment in one hour. Applied to the infected player’s eyes before a long rest, the ointment prevents the player’s condition from worsening. After 3 doses of the ointment, the player is cured.

Note: The Dungeon Master’s Guide doesn’t specifically state if the disease itself can be cured through magical means. Lay on of Hands and Lesser/Greater Restoration do specify they can cure one disease or ailment, but if you want to make this disease curable only with Sight Bright, it could add flavor and a neat side quest to bind the party together.

If blinded from Sight Rot, a player remains blinded until healed by magical means (the flower will NOT cure blindness). Blindness can be cured by a Lesser Restoration or Heal spell or by the Paladin ability Lay on of Hands.

(Note: If you want to make this more challenging, you can require a Greater Restoration spell) Healing Word and Cure Wounds have no effect on this disease.

Cackle Fever (The Shrieks)

Symptoms & Effects

Everyone loves a good laugh…until you can’t stop.

This disease targets humanoids, however, Gnomes are immune, and victims of this disease are often taken with fits of mad laughter. The book does not specify where this disease is found, but I would suggest the following:

  • In the lair/tower of a mad wizard that has been sealed off for years players notice a strange, slightly moldy smell.
  • A large, magically locked chest found deep in a cave depicts scenes of people writhing on the ground holding their sides. The rogue finally manages to unlock it, the box contains nothing but old, moldy clothes.
  • The party enters a seemingly deserted town. Suddenly, they see a person come out of a building, walking toward them, arms outstretched, laughing madly.
  • A villain knows he/she has been beaten, as he retreats, he throws a device that emits a strange smelling gas. Oddly, the gas has no immediate effect.

When exposed to Cackle Fever, players must succeed on a DC 10 Constitution Throw, on a failed save the effects of the disease manifest 1d4 hours later. An infected player gains one level of exhaustion that cannot be removed until the disease has been cured.

In addition, players with Cackle Fever must make a DC 13 Constitution Saving Throw anytime they experience stress (such as entering combat, taking damage, experiencing fear, having a nightmare, entering a dangerous area, etc.). On a failed save, the player takes 1d10 psychic damage and becomes incapacitated with mad laughter for 1 minute.

The player may repeat the saving throw at the end of its turn each round of combat to try to end the effect early. Any player that starts his/her turn within 10 feet of the laughing player must succeed on a DC 10 Constitution Saving Throw or become infected themselves.

Once a player succeeds on a saving throw against that individual’s laughter, he/she becomes immune to that individual’s laughter for 24 hours.

(If more than one member of the party is infected, the player is not immune to the other players mad laugh, but only the one he/she succeeded against.)

Cures for Cackle Fever

At the end of each long rest, the infected player must make a Constitution Saving Throw (DC 13), on a save, the DC saving throw for the mad laughter is reduced by 1d6. The disease is cured when the DC drops to 0. After three failed saves, the player gains 1 indefinite madness trait from the chart below, this effect becomes a permanent character flaw.

Cackle Fever can also be cured with a Greater Restoration spell or a Paladin’s Lay on of Hands ability. Cure Wounds and Healing Word have no effect.


There are many reasons why a player might slowly go insane. Such as making a deal with an evil entity in exchange for power, (if this sounds cool, see my post on making deals with devils!) losing someone close to them (although that NEVER happens. Haha..ha…..ha), or even just the stresses of daily adventuring, potentially deadly encounters, or a near death experience.

Whether it is a disease such as Cackling Fever (above), or witnessing a truly horrific event, players can suffer from various madness induced ticks, the effects of which can last from minutes to a lifetime.

When to Use Maddness

Although there are many reasons a player could go mad, it is still a serious effect that should not be used without careful consideration.

When your party experiences something truly horrendous, such as a human sacrifice or the slaughtering of an entire village, or if they encounter a spell or magical item that can break the psyche of the wielder, the player should roll a Wisdom or Charisma Saving Throw, with a DC based on the intensity of the event itself.

For example, if a player witnessed a dragon burning the village in which they grew up to the ground, the DC might be high (13-16) because of the personal nature of the atrocity; however, witnessing the slaughter of an Orc village to which the player has no connection might be lower, such as DC 8-10.

Types of Maddness

There are three main categories of madness: short term, long term and indefinite. Short term madness lasts 1d10 minutes, the effect is random based on the chart found on page 529 of the Dungeon Masters Guide.

d100 Effect (lasts 1d10 minutes)
01–20 The character retreats into his or her mind and becomes Paralyzed. The effect ends if the character takes any damage.
21–30 The character becomes Incapacitated and spends the Duration screaming, laughing, or weeping.
31–40 The character becomes Frightened and must use his or her action and Movement each round to flee from the source of the fear.
41–50 The character begins babbling and is incapable of normal Speech or Spellcasting.
51–60 The character must use his or her action each round to Attack the nearest creature.
61–70 The character experiences vivid hallucinations and has disadvantage on Ability Checks.
71–75 The character does whatever anyone tells him or her to do that isn’t obviously self-­destructive.
76–80 The character experiences an overpowering urge to eat something strange such as dirt, slime, or offal.
81–90 The character is Stunned.
91–100 The character falls Unconscious.

Long Term madness is a random effect from the chart found on page 260 of the Dungeon Masters Guide and lasts 1d10 hours.

d100 Effect (lasts 1d10 × 10 hours)
01–10 The character feels compelled to repeat a specific activity over and over, such as washing hands, touching things, praying, or counting coins.
11–20 The character experiences vivid hallucinations and has disadvantage on Ability Checks.
21–30 The character suffers extreme paranoia. The character has disadvantage on Wisdom and Charisma Checks.
31–40 The character regards something (usually the source of madness) with intense revulsion, as if affected by the antipathy effect of the Antipathy/Sympathy spell.
41–45 The character experiences a powerful delusion. Choose a potion. The character imagines that he or she is under its Effects.
46–55 The character becomes attached to a “lucky charm,” such as a person or an object, and has disadvantage on Attack rolls, Ability Checks, and Saving Throws while more than 30 feet from it.
56–65 The character is Blinded (25%) or Deafened (75%).
66–75 The character experiences uncontrollable tremors or tics, which impose disadvantage on Attack rolls, Ability Checks, and Saving Throws that involve Strength or Dexterity.
76–85 The character suffers from partial amnesia. The character knows who he or she is and retains Racial Traits and Class Features, but doesn’t recognize other people or remember anything that happened before the madness took effect.
86–90 Whenever the character takes damage, he or she must succeed on a DC 15 Wisdom saving throw or be affected as though he or she failed a saving throw against the Confusion spell. The Confusion effect lasts for 1 minute.
91–95 The character loses the ability to speak.
96–100 The character falls Unconscious. No amount of jostling or damage can wake the character.

Finally, indefinite madness lasts until cured. A random effect from the chart also found on page 260 which becomes a new character flaw.   

d100 Flaw (lasts until cured)
01–15 “Being drunk keeps me sane.”
16 – 25 “I keep whatever I find.”
26–30 “I try to become more like someone else I know—adopting his or her style of dress, mannerisms, and name.”
31–35 “I must bend the truth, exaggerate, or outright lie to be interesting to other people.”
36–45 “Achieving my goal is the only thing of interest to me, and I’ll ignore everything else to pursue it.”
46–50 “I find it hard to care about anything that goes on around me.”
51–55 “I don’t like the way people judge me all the time.”
56–70 “I am the smartest, wisest, strongest, fastest, and most beautiful person I know.”
71–80 “I am convinced that powerful enemies are hunting me, and their agents are everywhere I go. I am sure they’re watching me all the time.”
81–85 “There’s only one person I can trust. And only I can see this special friend.”
86–95 “I can’t take anything seriously. The more serious the situation, the funnier I find it.”
96–100 “I’ve discovered that I really like killing people.”

Cures for Madness

Calm emotions can subdue the effects of madness for a time, but it cannot cure long-term or indefinite madness. Lesser Restoration can cure short- and long-term madness but only a Greater Restoration spell can cure indefinite madness.

Note: Depending on the cause of the madness, you may choose to have no cure for the player’s madness or to make the cure harder to obtain, such as a Wish spell.

Creating Your Own Disease

If you want to create your own disease or use a common disease, such as malaria, use the following guidelines:

Incubation Time

How long does it take for your disease to take hold? Hours? Days? Weeks? Roll 1d4 or 1d6 to determine the minutes, days or weeks it takes for the symptoms to begin to appear. Also think about how the disease spreads and how quickly. Are others in danger of catching this disease from the infected player?


The most common symptoms for most diseases are fever, disorientation, and exhaustion. Depending on the disease, you can give the player penalties for ability checks requiring strength, wisdom, or dexterity.

For example, if the player is suffering from a disease that makes them feel weak, they would have a -1 or -2 penalty to all strength ability checks, depending on how long they have been sick. Likewise, a player suffering from a high fever that is making them delusional would have disadvantage on all perception checks.

Give your disease a tell-tale symptom, like Sight Rot’s bleeding from the eyes, or Cackling Fever’s mad laughter. It could be as simple as black veins spreading from a wound or coughing up blood. Whatever the symptom, it should get the player’s attention and be identifiable.

Symptoms should also worsen over time, eventually leading to a permanent effect or death. Saving throws are useful for determining if the player gradually gets better or worse, make sure to set a specific DC ahead of time. Common diseases should have low DCs while rare diseases should be much higher.

Curing the Disease

Don’t let your players use magic as a “get out of everything free” card. Some diseases are curses from the gods and, as such, cannot be cured with mortal magic. Other diseases are rare, or particularly aggressive, meaning players must find another cure before time runs out. What is the cure for your disease? Is there a cure?

Don’t be afraid to make the players seek out powerful Clerics or Paladins for a cure for the disease afflicting their friend. Perhaps the Cleric needs certain materials to craft a cure and the players must go gather what is needed before time runs out.

Diseases can be a great way to add threat and tension to the game without relying on combat. Depending on the size of the outbreak, a disease can even be a major plot point. Perhaps an angry lesser god has cursed a region with a disease until a stolen artifact has been returned to his shrine. Or a deadly, long extinct disease is released to wreak havoc on the world when the party opens a tomb which has been sealed for centuries. Monsters are fun, but nothing quite hits the heart and fears of a party like seeing first hand the devastation of an incurable disease.

I hope this has given you some ideas to add challenge and role-play to your game.

Until next time,

may your game have advantage, my friends!

-Halfling Hannah

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