Space adaptation syndrome, or space sickness, is what astronauts go through during adaptation to zero gravity. It is related to motion sickness, as the vestibular system adapts to free-fall.

Space sickness was effectively unknown during the earliest spaceflights, as these were undertaken in very cramped conditions; it seems to be aggravated by being able to freely move around, and so is more common in larger spacecraft. Around 60% of all Space Shuttle astronauts currently experience it on their first flight; the first case is now supected to be Gherman Titov, in 1960, who reported dizziness and nausea. However, the first significant cases were in early Apollo flights; Frank Borman on Apollo 8 and Rusty Schweickart on Apollo 9 both experienced identifiable and reasonably severe cases, in the latter case causing the mission plan to be modified.

As with motion sickness, symptoms can vary from mild nausea and disorientation to vomiting and intense discomfort; headaches and nausea are often reported in varying degrees. About half of sufferers experience mild symptoms; only around ten percent suffer severely. The most extreme reaction yet recorded was that felt by Senator Jake Garn in 1985; after his flight, NASA developed the "Garn scale" to measure reactions to space sickness. It runs from one to ten to cover most known cases; Garn himself rated thirteen. In most cases, it lasts two to four days.

Modern motion-sickness medication can counter space sickness, but is rarely used; it is felt that having astronauts adapt for a couple of days is better than them being drowsy and medicated for the duration of a mission. A general solution is now to ensure that any mission-critical activities (especially spacewalks, where vomiting could be fatal) are not planned in the first days of a mission; this allows crews to adapt and orient themselves properly.