Wearing face masks is recommended for the prevention of contracting or exposing others to cardiorespiratory infections, such as COVID-19. Controversy exists on whether wearing face masks during vigorous exercise affects performance. We used a randomized, counterbalanced cross-over design to evaluate the effects of wearing a surgical mask, a cloth mask, or no mask in 14 participants (7 men and 7 women; 28.2 ± 8.7 y) during a cycle ergometry test to exhaustion. Arterial oxygen saturation (pulse oximetry) and tissue oxygenation index (indicator of hemoglobin saturation/desaturation) at vastus lateralis (near-infrared spectroscopy) were assessed throughout the exercise tests. Wearing face masks had no effect on performance (time to exhaustion (mean ± SD): no mask 622 ± 141 s, surgical mask 657 ± 158 s, cloth mask 637 ± 153 s (p = 0.20); peak power: no mask 234 ± 56 W, surgical mask 241 ± 57 W, cloth mask 241 ± 51 W (p = 0.49)). When expressed relative to peak exercise performance, no differences were evident between wearing or not wearing a mask for arterial oxygen saturation, tissue oxygenation index, rating of perceived exertion, or heart rate at any time during the exercise tests. Wearing a face mask during vigorous exercise had no discernable detrimental effect on blood or muscle oxygenation, and exercise performance in young, healthy participants (ClinicalTrials.gov, NCT04557605).