This study examined potential sex differences in performance and perceived fatigability during a whole body endurance exercise performed under normoxia or moderate hypoxia. Nine males and eight females cyclists performed a 4-km cycling time trial under normoxia or hypoxia conditions. Performance fatigability and its central and peripheral determinants were measured via pre- to post-exercise changes in maximal voluntary isometric contraction (IMVC), voluntary activation (VA), and potentiated twitch force (TwPt) of knee extensors, respectively. Perceived fatigability was characterized via a rating of perceived exertion (RPE). Time to complete the trial was longer in hypoxia than normoxia in females (482 ± 24 vs. 465 ± 21 s) and males (433 ± 30 vs. 408 ± 31 s) (