Scientists writing in the Proceedings of the National Academy of Sciences say the findings suggest not all current astronauts would be suited to interplanetary travel.
The European Space Agency's 17-month Mars500 project, during which three Russian, two European and one Chinese volunteer crew members had only limited contact with the outside world, was intended to study the physical and psychological effects the long journey to Mars might have on astronauts.
A sleep study conducted during the simulated mission indicated astronauts for such missions should be tested for their ability to deal with changes in their natural day/night cycle, researchers said.
"This illustrates that there are huge differences between individuals and what we need to do is select the right crew, people with the right stuff, and train them properly," said Mathias Basner of the University of Pennsylvania, who was involved in the sleep study portion of the research.
One crew member lost his natural day/night rhythm completely, slipping into a 25-hour day that after 12 days had him completely out of sync with his crewmates, the researchers said.
"You can imagine that that would not be good during a real Mars mission when there are mission critical tasks planned during the day," Basner told BBC News.
The affected crew member became somewhat isolated from his companions, finding himself the only person awake as the others slept, researchers said.
Another crew member developed a mild depression, they said.