INTRODUCTION: Males and females differ anatomically and functionally in cardiorespiratory regulation, with males tending to experience greater oxygen desaturation under hypoxia. Therefore, sex might moderate cardiorespiratory responses to acute hypoxia exposure. Accordingly, we hypothesized that sex differences in cardiovascular and ventilatory responses would be more pronounced with equal hypoxia duration (iso-time) but less pronounced at similar oxygen desaturation levels (iso-saturation). METHODS: Twenty-two (12 females) healthy individuals were exposed to normoxia (10 min at FiO RESULTS: At 10 min of hypoxia (iso-time), males desaturated more than females (interaction: CONCLUSION: Our data indicate that females counterbalance hypoxia mainly by systemic circulatory adjustments, while males use both, circulatory and ventilatory adjustments.