Two players can play Resident Evil 5 cooperatively in its main campaign.
Resident Evil 5 was designed around two-character cooperation. Chris Redfield is paired with Sheva Alomar, and a second player can control Sheva while the first controls Chris. If played alone, the computer controls Sheva instead.
The campaign supports cooperative play through its story chapters, combining combat, item management, and coordinated actions. Some encounters and puzzles are structured around the two characters working together, although the game remains playable as a single-player experience.
This two-player limit applies to the main campaign’s cooperative structure, not to every mode or release feature. Resident Evil 5 also includes additional content and competitive modes that have their own rules. It is therefore more precise to answer two rather than simply describing the game as multiplayer.