Isaac's dead cat, Guppy, surrounded by flies.
Upon pickup, Isaac's health is set to one Heart Container, and he is given 9 lives along with a cosmetic cat head familiar. His health can be increased as normal, but it will reset to 1 heart container upon death (unless the maximum heart containers went off-screen, in which case, Isaac will respawn with those extra heart containers).
- When combined with two other Guppy items (Guppy's Tail, Guppy's Head or Guppy's Paw), Isaac will turn into Guppy. He will also gain The Mulligan effect and flight.
- When Dead Cat is picked up and the player only has Soul Hearts (with the exception of ???), Dead Cat actually gives the player a permanent red heart container and does not take away the previously obtained Soul Hearts. This is useful if, for example, a Devil deal has left the player with no red hearts - Dead Cat essentially becomes a HP item!
- It's possible to pick up two Dead Cats in a Curse Room by opening a Red Chest, not picking up Dead Cat, and then opening the other Red Chest. Picking up a second Dead Cat will reset Isaac's lives back to 9 and reset heart containers to 1.
- If Ankh is picked up after Dead Cat, the next time you die you will become ??? with 4 soul hearts no red hearts per Ankh's effect. If you die again, you will return to being your original character with one red heart.
- Guppy's Paw - Dead Cat has good synergy with Guppy's Paw, as each life effectively means three spirit hearts for a total of twenty-seven spirit hearts. As such, it is a good idea to hang onto Guppy's paw if Dead Cat is already collected.
- After defeating a boss, Isaac can kill himself with a Bomb or something similar, respawn outside the Boss Room, and fight the boss again for another item. Items that appear after defeating the boss can either be picked up or left in place (for items that increase heart containers it is generally better to leave them in place, since heart containers are reset to one on death by Dead Cat, and you can pick up all of these items at once after you are done). This can be repeated as long as you have enough lives. Killing bosses like It Lives and Mom's Heart with each life will also count as beating the game that many times.
- Doing this can possibly turn the boss into its Champion version, since it is determined upon entering the room.
- If the first boss in an XL floor is a Harbinger, killing yourself, respawning, and then entering the boss room again will show the incorrect Boss vs. screen picture, and the reward will be an item from the next boss' pool.
- Using this method on a Harbinger while not in an XL floor will make Cube of Meat spawn multiple times, which can give the player 2 fully formed meat boys if all 8 lives are used on that boss.