Purpose Capsaicin (CAP) has been demonstrated to activate the transient receptor potential cation channel subfamily V member 1 (TRPV1), which can regulate nitric oxide production and, consequently, affect oxygen delivery to the muscles. In addition, TRPV1 activation can lead to calcium release from the sarcoplasmic reticulum, which is crucial for optimal force development. Therefore, this study aimed to evaluate the effect of a single dose of capsaicin on leg extension exercise performance and skeletal muscle oxygenation (SmO2) during exercise and exercise recovery in physically active individuals. Methods In a randomized, double-blind, crossover study, eight males ingested 12 mg of CAP or maltodextrin as a placebo (PLA). Forty-five minutes after supplementation, the participants performed three sets of leg extension exercises at 70% of 1 repetition maximum, and the number of repetitions was evaluated. During exercise and exercise recovery, SmO2 parameters were recorded. Plasma lactate was analyzed before supplementation, immediately, and 10 min after exercise. Results There were no changes in SmO2 parameters (p textgreater 0.05) and the number of repetitions (p textgreater 0.05) throughout the three sets of leg extensions. Additionally, a medium (d = 0.67), large (d = 0.83) and small (d = 0.31) effect size was observed in resaturation rate during set 1, set 2, and set 3 recovery. Plasma lactate increased significantly (p textless 0.05) immediately after exercise in both CAP and PLA groups without significant changes between the groups (p textgreater 0.05). Conclusion A single dose of capsaicin did not change SmO2 parameters and muscular performance during resistance exercise in physically active individuals.