Leg- vs arm-cycling repeated sprints with blood flow restriction and systemic hypoxia Abstract Purpose The aim was to compare changes in peripheral and cerebral oxygenation, as well as metabolic and performance responses during conditions of blood flow restriction (BFR, bilateral vascular occlusion at 0% vs. 45% of resting pulse elimination pressure) and systemic hypoxia (~ 400 m, FIO2 20.9% vs. ~ 3800 m normobaric hypoxia, FIO2 13.1 ± 0.1%) during repeated sprint tests to exhaustion (RST) between leg- and arm-cycling exercises. Methods Seven participants (26.6 ± 2.9 years old; 74.0 ± 13.1 kg; 1.76 ± 0.09 m) performed four sessions of RST (10-s maximal sprints with 20-s recovery until exhaustion) during both leg and arm cycling to measure power output and metabolic equivalents as well as oxygenation (near-infrared spectroscopy) of the muscle tissue and prefrontal cortex. Results Mean power output was lower in arms than legs (316 ± 118 vs. 543 ± 127 W; p < 0.001) and there were no differences between conditions for a given limb. Arms demonstrated greater changes in concentration of deoxyhemoglobin (∆[HHb], − 9.1 ± 6.1 vs. − 6.5 ± 5.6 μm) and total hemoglobin concentration (∆[tHb], 15.0 ± 10.8 vs. 11.9 ± 7.9 μm), as well as the absolute maximum tissue saturation index (TSI, 62.0 ± 8.3 vs. 59.3 ± 8.1%) than legs, respectively (p < 0.001), demonstrating a greater capacity for oxygen extraction. Further, there were greater changes in tissue blood volume [tHb] during BFR only compared to all other conditions (p < 0.01 for all). Conclusions The combination of BFR and/or hypoxia led to increased changes in [HHb] and [tHb] likely due to greater vascular resistance, to which arms were more responsive than legs.