A habitat atmosphere of 34% oxygen (O2) and 66% nitrogen (N2) at 8.2 psia (56.5 kPa) is proposed to minimize the risk of decompression sickness during extravehicular activity. The resulting inspired O2 partial pressure (PIo2) of 128 mmHg is similar to that experienced during portions of 41 Space Shuttle missions that used a "staged" denitrogenation (prebreathe) protocol with an atmosphere of 26.5% O2 and 73.5% N2 at 10.2 psia (70.3 kPa). We evaluated symptoms possibly linked to mild hypoxia in astronauts breathing a PIo2 of 127 mmHg. Environmental data were used to determine time in the shuttle at 10.2 psia and time at 14.7 psia (101.3 kPa). A total of 14 possible hypoxia symptoms were compared with symptoms collected during normoxic shuttle operations at 14.7 psia using logistic regression. There were 134.1 d (788.8 person days) under the 10.2 psia staged condition with a mean of 3.17 ± 2.2 SD d/mission. There were 258.81 d at 14.7 psia (2192.95 person days). An average of 4.31 potentially hypoxia-related symptoms per mission day was documented under the staged condition compared with 4.08 per mission day during the normoxic condition. Logistic regression showed no symptoms were significantly associated with just the 10.2 psia condition. Chronic exposure to a PIo2 of 127 mmHg is well-tolerated by healthy humans on Earth. A similar short-duration exposure on the shuttle resulted in no increased reporting of possible hypoxia-related symptoms. However, chronic mild hypoxia interactions with physiological changes due to microgravity adaptations remain unclear.Wessel JH III, Schaefer CM, Thompson MS, Norcross JR, Bekdash OS. Retrospective evaluation of clinical symptoms due to mild hypobaric hypoxia exposure in microgravity. Aerosp Med Hum Perform. 2018; 89(9):792-797.