BACKGROUND: Some endurance athletes exhibit exercise-induced arterial hypoxemia during high-intensity exercise. Inhalation of hyperoxic gas during exercise has been shown to counteract this exercise-associated reduction in hemoglobin oxygen saturation (SaO2), but the effects of hyperoxic gas inhalation on performance and SaO2 during high-intensity intermittent exercise remain unclear. This study investigated the effects of hyperoxic gas inhalation on performance and SaO2 during high-intensity intermittent cycling exercise. METHODS: Eight male cyclists performed identical intermittent exercise tests (five sets of 3-min high-intensity cycling alternated with 3-min active recovery periods) under two different inspired air conditions, hyperoxia (HO; FIO2 = 0.36) and normoxia (NO; FIO2 = 0.21). The fifth set of each test was terminated at exhaustion, and the exercise time to exhaustion was recorded. Variables associated with arterial oxygen saturation (SpO2) were measured using an ear pulse oximeter. RESULTS: Time to exhaustion under HO conditions was significantly longer than under NO conditions (34.9 ± 4.6 vs. 30.0 ± 2.5 min, P = 0.004, ES = 1.32). SpO2 was maintained under HO conditions but decreased under NO conditions. CONCLUSIONS: Hyperoxic gas inhalation during the entire high-intensity intermittent exercise enhanced exercise performance in male cyclists.