Best Diseases To Use As A DM In Dungeons & Dragons

Across the many sourcebooks and adventure modules, Dungeons & Dragons has dozens of diseases that contain a variety of effects and ways to cure them. One way a DM can introduce plot hooks, adventure rewards, or character development is by spreading plague and misery.



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With the many diseases available, some are better suited to certain environments or for specific adventuring themes. Whichever way you plan to develop your campaign, there will be a disease that is right for it while adding additional stakes. Just make sure to consider your players as to not cross any personal boundaries they might have towards the subject.

10 Let Your Players Cure Disease

A man being fed a healing potion
Potion of Healing by Pauline Voss

Although being able to gleefully describe how your players develop blue boils across their body or how they are overcome with a cackling madness that incapacitates them, your players can survive with spells like Lesser Restoration, Heal, or Hero’s Feast and class abilities from Transmutation wizards and paladins.

Ensure that if your players choose one of these abilities, you intend to infect them with a disease. Otherwise, that player will regret choosing an ability that never gets used. Infecting your players isn’t about hurting them for no reason, but adding additional challenges that require time and resources to resolve.

9 Sight Rot

A blue feminine sea creature smiles wickedly over some shell
Sea Hag by Andrea Piparo

Sight Rot is an especially obvious disease as it causes you to bleed from your eyes and lose your vision over the course of five days. Humanoids contract Sight Rot by drinking tainted water sources, which is the perfect opportunity for plot hooks involving a village’s well poisoned by certain NPCs or evil factions.

Sight Rot also gives your players an opportunity for role play as they slowly lose their vision, which can help them get into character or establish motivations and alignment. Another interesting aspect of Sight Rot is it gives a specific, rare flower that has the power to cure it, called Eyebright, which can be the basis for a whole adventure.

8 Sewer Plague

Rust Monster runs past adventurer and rusts sword
Rust Monster by Simon Dominic 

Contracted from animal bites like spiders or rats that live in sewers and swamps, Sewer Plague slowly increases exhaustion levels until they succeed Con saves or die. By remembering this disease every time your players wade through one of these iconic D&D environments, you can start to add low CR creatures packed with deadly punches.

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This can also be a way to reward players with a high AC or passive perception as they will be able to avoid the plagued rat skulking behind refuse. In this way, you add additional challenges rather than just increasing the CR of monster encounters or adding more traps.

7 Cackle Fever

Warlock touched by shadow eldritch powers
Herald of Hadar by Valera Lutfullina 

As the name implies, Cackle Fever causes its victims to laugh uncontrollably in a fit of madness. Anyone within ten feet of someone cackling with the disease can also contract it.

This is the kind of disease best suited for a horror campaign or adventure in settings like Barovia.

Because the disease only manifests during periods of stress or heightened fear, this can lead to some interesting role-play moments between you and your players that can enhance the spooky atmosphere. If your players are especially avoidant of the disease, they might be afflicted with indefinite madness which you can use as a plot hook for a larger adventure.

6 Bluerot

armored skeletons reach forward necromancy
Clattering Skeletons by Aleksi Briclot 

Introduced in Ghosts of Saltmarsh as a unique attack for undead creatures, Bluerot covers the diseased in blue boils that will eventually kill them. The additional mechanical effects are vulnerability to radiant damage but the ability to breathe underwater, which makes Bluerot unique as the only disease with a benefit.

Since this disease is associated with undead creatures, you can apply this attack to any zombie-like stat block to make them more dangerous or to surprise more experienced players. Bluerot allowing the ability to breathe underwater is useful as a storytelling tool to perhaps give insight into a strange fishing village or ship crew.

5 Mad Monkey Fever

Zombie coming out from behind a stone wall
Dungeon Crawler by Svetlin Velinov

Passed to the host through a magic, blue mist, Mad Monkey Fever gives your players the effects of long-term madness for up to 100 hours. This is best used as a dungeon trap, barring passageways or surrounding important puzzle pieces that can only be removed via Dispel Magic.

The long-term madness table in the DMG can have some debilitating effects and your players don’t even have to breathe in the mist to contract it, so make sure to reserve this for high-level adventures. Otherwise, be prepared for some unique interactions when they can no longer speak or develop severe amnesia.

4 Throat Leeches

hooded figure holding their bloody wrist as they attach a decrepit looking hand to it
Hand of Vecna by Irina Nordsol

Contracted by ingesting water infested with parasites, Throat Leeches host in your player’s throat until they die of exhaustion. This disease is perfect for survival adventures that put focus on your player’s resourcefulness and resource management.

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Because Throat Leeches can be avoided by drinking boiled water or rainwater, consider how an evil NPC might infect water sources or even poison the drinks of your players or other important characters. Since Throat Leeches are easy to avoid and remove, consider using them on low-level parties.

3 Contagion Spell

spellcaster shooting purple lightning at another character in a purple void
Ray of Enfeeblement by Campbell White

The only spell that allows you to inflict disease personally, Contagion gives you access to a handful of diseases that prioritize an immediate, mechanical effect. Since the spell establishes the effects as a disease, spells like Lesser Restoration or a Paladin’s Lay on Hands ability will still remove it, but eats up actions in combat.

This spell is best given to evil NPCs or even BBEGs that seek to spread the plague across the world. Since the effects last up to seven days, it can be used to halt your players from reaching their goal or force them to use resources to avoid being at a disadvantage when exploring or in combat.

2 Rutterkin

sepulcher ghoul
Sepulcher Ghoul by Jason Engel

Rutterkin are demons with a unique attack that inflicts a disease that transforms the infected into an abyssal wretch with its own stat block. Despite being a low challenge rating, this makes Rutterkin especially dangerous with low-level parties that don’t have access to Lesser Restoration.

If you’d rather use aberrations instead of fiends, the Slaad also have this disease effect of transforming its targets into more Slaad. This is a very punishing disease as it essentially kills your player’s characters without them making death saves and without the option to revive with normal means, so only use it if you know your players would accept it.

1 Zuggtmoy

dungeons & dragons zuggtmoy
Zuggtmoy by Tyler Jacobson

As one of the abilities of the demon lord, Zuggtmoy, she can release spores that cause a disease that inflicts madness and can eventually transform creatures into undead spore servants. Since Zuggtmoy is a CR 23 creature, it is unlikely your party will be facing her without the tools to easily overcome this disease, but because of its nature, you can apply it in a number of unique ways.

For instance, spore traps and mushroom colonies can contain spores of Zuggtmoy, and if activated by your players, will slowly cover them in fungal growth and turn them into a zombie. While perfect for a The Last of Us-themed campaign, it can be used for any underground dungeon trap. Just make sure to adjust the save DC according to your player’s level.

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