Dead Space Ignition is a followup to Dead Space 2, set between the two main games. The game takes the form of what executive producer Steve Papoutsis describes as an "interactive comic-style game" and is written by Antony Johnston, the writer of the Dead Space games and comic book series.

An engineer named Franco Delile and his partner Sarah are called to fix an elevator on the Sprawl (a space station of a shard of Titan, one of Saturn's moons that was "planet-cracked"), only to discover evidence of sabotage. They are then called to fix a computer mainframe, again finding that the damage was intentional. While traveling between jobs, they hear distant screams and investigate, only to encounter people being attacked by grotesque monstrosities dubbed "Necromorphs." Franco and Sarah escape using the tram. From there on, they are sent across the Sprawl in an increasingly desperate attempt to repair station systems and assist other survivors, all the while under attack by Necromorphs. Depending on the player's choices, Sarah may be killed by asphyxiation, Necromorphs, or by Franco after receiving a coded message; he may be a Unitologist. The story ends with Franco reaching the Sprawl hospital, and reviving the comatose Isaac Clarke, leading up to the opening scene of Dead Space 2.