OBJECTIVE To compare the acute performance and psychophysiological responses of repeated cycling sprints to exhaustion with a short exercise-to-rest ratio (1:6), between different effort durations and inspired oxygen fractions. METHODS On separate visits, 10 active participants completed 6 repeated cycling sprint exercises to exhaustion with 3 different effort durations (5, 10, and 20 s) and 2 conditions of inspired oxygen (20.9% and 13.6%). Exercise-to-rest ratio was 1:6 for all trials (ie, 5:30, 10:60, and 20:120). Vastus lateralis muscle oxygenation (near-infrared spectroscopy), blood lactate concentration, and lower-limb and breathing discomfort, using ratings of perceived exertion, were measured. RESULTS Number of sprints and peak power output decreased while blood lactate increased (all P < .001) during 5:30 compared with 10:60 or 20:120. No condition or interaction effects were reported for blood lactate and exercise-related sensation. Muscle deoxyhemoglobin increased (P < .001) and total hemoglobin decreased (P = .002) during sprint with increasing sprint duration (no condition or interaction). CONCLUSIONS During repeated-sprint exercise to exhaustion with a short exercise-to-rest ratio, the psychophysiological responses did not differ between normoxia and moderate hypoxia, probably due to an extended recovery period. It means that hypoxia did not modify repeated-sprint exercise performance with a short exercise-to-rest ratio. The sprint duration was the primary underlying factor of the observed differences in performance and muscle oxygenation reported between the repeated-sprint exercise sessions.