Objective: The aim of this study was to determine the effects of sprint interval exercises (SIT) conducted under different conditions (hypoxia and blood flow restriction [BFR]) on mechanical, cardiorespiratory, and muscular O ₂ extraction responses. Methods: For this purpose, 13 healthy moderately trained men completed five bouts of 30 s all-out exercises interspaced by 4 min resting periods with lower limb bilateral BFR at 60% of the femoral artery occlusive pressure (BFR ₆₀ ) during the first 2 min of recovery, with gravity-induced BFR (pedaling in supine position; G-BFR), in a hypoxic chamber (FiO ₂ ≈13%; HYP) or without additional stress (NOR). Peak and average power, time to achieve peak power, rating of perceived exertion (RPE), and a fatigue index (FI) were analyzed. Gas exchanges and muscular oxygenation were measured by metabolic cart and NIRS, respectively. Heart rate (HR) and peripheral oxygen saturation (SpO ₂ ) were continuously recorded. Results: Regarding mechanical responses, peak and average power decreased after each sprint (p < 0.001) excepting between sprints four and five. Time to reach peak power increased between the three first sprints and sprint number five (p < 0.001). RPE increased throughout the exercises (p < 0.001). Of note, peak and average power, time to achieve peak power and RPE were lower in G-BFR (p < 0.001). Results also showed that SpO ₂ decreased in the last sprints for all the conditions and was lower for HYP (p < 0.001). In addition, Δ[O ₂ Hb] increased in the last two sprints (p < 0.001). Concerning cardiorespiratory parameters, BFR ₆₀ application induced a decrease in gas exchange rates, which increased after its release compared to the other conditions (p < 0.001). Moreover, muscle blood concentration was higher for BFR ₆₀ (p < 0.001). Importantly, average and peak oxygen consumption and muscular oxyhemoglobin availability during sprints decreased for HYP (p < 0.001). Finally, the tissue saturation index was lower in G-BFR. Conclusions: Thus, SIT associated with G-BFR displayed lower mechanical, cardiorespiratory responses, and skeletal muscle oxygenation than the other conditions. Exercise with BFR ₆₀ promotes higher blood accumulation within working muscles, suggesting that BFR ₆₀ may additionally affect cellular stress. In addition, HYP and G-BFR induced local hypoxia with higher levels for G-BFR when considering both exercise bouts and recovery periods.