Contagion is a multiplayer focused game with 3 different game modes; Hunted, Escape, and Extraction. Hunted, which supports up to 16 players, is a free-for-all "deathmatch" game mode in which players fight each other, while A.I.-controlled zombies wander the level and serve as an environmental hazard. When a player is killed, they respawn as a zombie and can participate alongside the A.I.-controlled zombies in attacking the surviving players. The goal of the game is to be the last living player. Escape is a cooperative game mode in which a team of up to 8 players is tasked with progressing through a level, fighting through zombies while completing various mission objectives in a linear order with the ultimate goal of escaping the map.

In both game modes, when a player is killed they respawn as a zombie and are tasked with helping the A.I.-controlled zombies hunt down the remaining human players. Player-controlled zombies are faster and more maneuverable than A.I.-controlled zombie enemies and therefore present a greater threat to human players. Both Escape and Extraction can be played off-line by a single player, although they are geared towards multi-player gameplay.