Introduction: Blood flow restriction (BFR) exercise has emerged as a method of increasing muscle size and strength with low intensity resistance training. While the cuff pressures used during BFR are typically a percentage of resting arterial occlusion pressure (AOP), the impact these cuff pressures have on blood flow during lower body exercise is unknown. Purpose: To determine how various cuff pressures impact blood flow and tissue perfusion during exercise. Methods: Eleven healthy male participants completed four sets of knee extension (30 reps per set at 30% max torque) with 0%, 60%, 80%, and 100% of arterial occlusion pressure (AOP) was applied to the proximal portion of the thigh. Femoral artery blood flow, tissue oxygenation, and central hemodynamics were continuously recorded before, during, and after exercise. Electromyography (EMG) amplitude was recorded from the vastus lateralis during exercise. Results: Blood flow increased during exercise compared to rest across all cuff pressures (p < 0.001), however compared to 0%, the absolute blood flow was reduced by 34 ± 17%, 45 ± 22%, and 72 ± 19% for 60, 80, and 100% AOP, respectively. Furthermore, each cuff pressure resulted in similar relative changes in blood flow before, during, and after exercise. During exercise, tissue saturation index (TSI) decreased as cuff pressure increased (p ≤ 0.005) with the exception of 80 to 100% AOP. Deoxyhemoglobin increased (p ≤ 0.001) with cuff pressure. Conclusion: Our data indicate that while BFR knee extension elicits an absolute hyperemic response at cuff pressures up to 100% resting AOP, the relative reductions in blood flow are consistent across rest, exercise and recovery.