Two astronauts, Bower and Payton, wake to find themselves drifting through space 500 million miles from Earth and with no memory of who they are, what they are doing, or what has happened to the crew of their 60,000 passenger sleeper ship the Elysium. They are unable to access the ship's bridge, and cannot communicate with any other members of the crew, including the flight team they are to relieve.[4] While exploring the spacecraft under Payton's radio guidance, Bower encounters several other surviving crew members, and the astronauts start to learn that a terrible event has occurred on board which might have affected the survival of the entire human species.[5]


As Bower ventures deeper into the ship, he discovers other humans running from monsters that are former crew members endowed with genetic enhancements meant to help them adapt to their eventual new world, but which instead caused them to mutate to the spacecraft environment. They also learn that some crew members also suffer from a psychosis - a severe psychological condition called Pandorum - which can be brought about by being in deep-space for extended periods of time, and is triggered to an uncontrollable level by intense emotional trauma. Those afflicted with Pandorum experience severe paranoia, vivid hallucinations - and eventually homicidal rage.


Their mission is revealed to be one of desperation. Earth, suffering from massive overpopulation, dispatched the sleeper ship and its crew on a 120-year voyage to a new, Earth-like planet to create a settlement. To add even more weight to their mission, one of the survivors whom Payton discovers, Gallo, reveals to him that he was part of the flight crew that receives a message from Earth, stating that the planet had been destroyed and the people on board the ship are the last humans. At that moment, Gallo had snapped and succumbed to Pandorum, killing the other crew members with him. Since then, he has been playing God, exiling awakened crew members and passengers to the storage hold, which is where they began to mutate and adapt to the ship's environment. By now, most of the 60,000 person crew is either dead or mutated.