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The two astronauts Bower and Payton wake up in a spaceship called "Elysium" from an artificial deep sleep, which resulted in a temporary memory loss. You know at first neither where they are nor what their real mission. It is not possible for them to contact the bridge or other crew members. Also, they are not capable of the district in which they have woken up from deep sleep to leave through the lock.
While attempting to obtain by other means access to the bridge, Bower pushes ever further into the spaceship that appears to be driving with almost no energy in the universe and is subject to periodic power fluctuations. Payton directs him by radio from a command console that could both operate. Gradually, Bower finds dead bodies and survivors, only to find that there are also non-human-looking, aggressive creatures on board, people hunt and feed on them.
The small group of survivors - except Bower nor the biologist Nadia, the agricultural workers Manh and the chef Leland - begins to wade into the reactor of the ship, which is nearing failure and causes the energy fluctuations. Leland, who initially tried to eat the other survivors, they learn that the earth was destroyed shortly after the launch of the spacecraft and thus they are the last survivors of the human race aboard a colony ship. The aim of the mission is to colonize after 123 years of flight the Earth-like planet Tanis, since the earth was suffering from extreme overpopulation. As a theory of the existence of the creatures told Leland that a crew member has been playing as a god. This has some of the crew and passengers alert and released. Due to an artificial Anpassungsmutagen, which was originally designed for the rapid adaptation of the colonists at Tanis, but it led to the adaptation to the struggle for survival in the Elysium defective, mutated the colonists to the creatures. Also suffer from some crew members on board a disease caused by the long space flight psychosis, called Pandorum. Those affected suffer from extreme paranoia and vivid hallucinations.
Meanwhile, Payton finds another survivor, Gallo, who seems to suffer from Pandorum and is extremely suspicious of Payton. Hysterical Gallo tried to leave the ship, because he also recognized the threat of reactor failure. Payton learns that Gallo at the time was on duty on the bridge when the news arrived of the destruction of the earth. In a battle between the two Gallo merges before Payton's eyes with his own, and Payton is aware that Gallo was only his second incarnation itself, which he has imagined in his Pandorum-delusion.
However, it is possible Bower, to restart the reactor and thus fully restore the power supply for the boat. Chased by the creatures the small group of survivors fled back to the bridge and Payton to regain control of the ship.
Once there, Bower and Nadia find that the Elysium long ago arrived at the destination planet, where the time automatically ended and now lies on the ocean floor for 900 years. Bower knows by now by returning reminder that the alleged Payton Payton is not his superior. It turns out that Payton is actually Gallo is suffering since the news of the sinking of the earth from delusions and killed his former comrades and probably also that God was playing crew member of the Leland told. The last fight on the ship in the meantime also suffering from symptoms of Pandorum Bower damaged the hull, the ship is flooded and drowned Gallo on the bridge. At the last second and Nadia Bower can by means of its Hyper cabin, which also serves as a rescue capsule to save the ship and float to the water surface.
By the rupture of the shell, the automatic evacuation is started from the onboard computer, are shot at the sea surface through which all further situated in a deep sleep people with their escape pods.
Finally, at the end of the colonization of new planets begin with the 1213 survivors - from the original 60,000.