Death's Heads are invulnerable, flying enemies that move diagonally around the room and deal contact damage. They will bounce off of Isaac, walls, and each other, generally causing chaos in a room. They immediately die when the room is cleared. They can be killed if hit with the Chaos Card, Little Horn, or Euthanasia.
Dank Death's Head
Dank Death's Heads behave the same as regular Death's Heads, but are vulnerable and must be killed to clear a room.
Flesh Death's Head
Flesh Death's Heads are vulnerable, but do not need to be killed to clear a room. They release six blood shots upon death or upon clearing the room.
Cursed Death's Head
Cursed Death's Heads behave the same as regular Death's Heads but have a purple aura around them. If Isaac enters the aura, he will be inflicted with the fear status effect for around two seconds, unable to fire tears for the duration of the effect.
Brimstone Death's Head
Brimstone Death's Heads behave the same as regular Death's Heads in terms of movement. When Isaac comes into their line of sight, they will pause for a moment with a faint laser as a slight warning of where they are about to fire, and proceed to blast a beam of Brimstone.
Dusty Death's Head
Dusty Death's Heads behave uniquely to other Death's Heads- they continuously travel across the screen oscillating up and down, going off-screen and reentering on the opposite side. They are invulnerable and are destroyed once the room is cleared.
Redskulls act similar to Death's Heads except that they can release out a ring of fire that damages Isaac and can also ignite certain enemies like the Rock Spider. And much like the Flesh Death's Heads, they can be killed before clearing the room.
Ultra Death Head
Ultra Death Heads behave uniquely to other Death's Heads and more similarly to Dusty Death Heads, oscillating up and down in large wave-like patterns, going off-screen and reentering on the opposite side. They are summoned in a horde as a part of one of Ultra Death's attacks and are invulnerable, only being destroyed at the end of the attack.
- Death's Head, Flesh Death's Head, Stonies, Cross Stonies, and Eggies are the only non-boss enemies with a death animation.
- In the game's files, the Dank Death's Head has a death animation that is impossible to see because it needs to be killed to clear a room.
- The Flesh Death Heads' death animation only plays if they die when the room is cleared. If they are killed, they will simply create a blood explosion.
- The Death's Head is based on the Bubble from The Legend of Zelda on the NES, as they are both skulls that are usually invulnerable which maneuver by bouncing off of walls.
- The Dusty Death's Head is based on the Medusa Head, as both fly in a wave-like pattern that is intended to be difficult to dodge.
- In a closet room in Womb, there is a room with 1 Red Poop, 4 Blood Donation Machines, and 4 Flesh Death's Heads. When entering the room, they appear to die quickly since no other enemies in the room exist there.
- If a Death's Head is permanently charmed by charming a Void in Chapter 3, it cannot interact with enemies or enemy tears and will simply fly around the room.
- Prior to Booster Pack #5, if Death Heads were in the process of dying, they could still damage Isaac.
- In Antibirth, Cursed Death's Heads were called Smokys.
- Cursed Death's Heads resemble The Heretic.
- Redskulls have a stray pixel on the top-right of their sprite which does appear in-game, and is animated similar to their fire.
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