The biopsies, taken 45 days before launch and on the day of return, showed dramatically how muscles atrophy in zero gravity.
The losses in fiber mass, force and power translated into a decline of more than 40 percent in the capacity for physical work, Fitts reported.
Ironically, beefing up before the trip had no impact on muscle loss. In fact, crew members who began with the biggest muscles turned out to have the biggest decline in muscle fitness.
Under one NASA scenario, a return trip to Mars using current rocket technology would take around three years, if a one-year stay on the planet is factored in.
If so, the decline in the most-affected muscles such as the calf could approach 50 percent, said Fitts.
Astronauts would tire faster doing even routine tasks, especially if they donned a space suit, and on returning to terrestrial gravity they could be so weak they might be unable to evacuate their spacecraft quickly in an emergency.
The paper has been published online by The Journal of Physiology, and will appear in print next month.