Blob Mode is a game mode in which the crew of Space Station 13 must remove a rapidly spreading, extremely destructive green Blob from the station. The station's AI must prevent anyone from leaving in this mode, and must also help the crew fight the blob off. Should the crew fail to destroy the blob after either a certain amount of time has elapsed or the blob has spread too far, the station will self-destruct, causing both the crew and the AI to lose the game.

The blob can be "hurt" in several ways. The simplest is to take an activate blow torch and attack the blob. This will weaken/kill the square of blob attacked. The blob's growth is hampered by direct contact with space. The blob is highly susceptible to fire, although the direct approach of emptying a canister of plasma and then setting it on fire can backfire due to the blob's ability to grow by absorbing plasma. The best way is to set off small bombs which don't release enough plasma to make it grow. Flashbangs are a tried and true method of mass blob containment. Be sure to stand back after throwing them though.