Three years after the events of Dead Space, Isaac Clarke awakens in the hospital of the Sprawl, a human colony orbiting Saturn. Faced with another Necromorph outbreak, Isaac must shed his restraints and recover his equipment before finding a way to escape the city. Aided by the mysterious Daina, Isaac navigates through the hospital while encountering numerous enemies, including a Tripod, as well as Nolan Stross, a fellow psychiatric patient.