Aliens: Colonial Marines featured a campaign with many dynamic drop-in/drop-out cooperative multiplayer for up to 4 players online or 2 players locally via split screen. A deathmatch 6 v 6 mode is available, as well as a 4 v 4 objective mode called Escape, in which the marines team reach an evac point while the alien team must hunt and stop them. The PC version contains no campaign offline cooperative mode.

Multiplayer skins based on four colonial marine characters from the movie Aliens were included in post-order editions of the game according to Sega's original page. These include corporal Dwayne Hicks, smartgun specialist Mark Drake, sergeant Al Apone and private William Hudson.

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