Athletes use sports supplements for various reasons. Capsaicin supplementation appears to improve muscle performance and conserve muscle glycogen and recovery. This study aimed to investigate the effect of capsaicin supplementation on physical fatigue and athletic performance after a period of training in young female volleyball players. The subjects of the present study were female volleyball players, aged 18 to 23 years. From these subjects, 18 were selected as a sample and tested. These subjects were divided into two groups: (1) capsaicin supplement group and (2) placebo group. The subjects in the first group received capsaicin supplement daily in the form of capsules containing 500 mg of capsaicin extract and performed their sports activities in the sports club. Before taking the supplement and placebo, sports tests of pull-ups, sit-ups, 20-meter run, 9x4 run, and Sargent jump were performed and recorded to measure athletic performance. Blood was also drawn from them and creatine phosphokinase, glucose, nitrogen, ammonia, and lactate dehydrogenase factors were tested to measure physical fatigue. Finally, after eight weeks of supplement and placebo use, all of the aforementioned tests that were taken from the subjects on the first day were repeated and all results were recorded. The data were analyzed using a dependent t-test and an independent t-test between groups. The results of the present study showed a significant decrease in the levels of creatine phosphokinase, nitrogen and lactate dehydrogenase in the blood in the intra-group comparison and a significant increase in blood glucose concentration and ammonia levels in the capsaicin supplement group in the post-test compared to the pre-test. Also, physical performance indicators such as the number of pull-ups, sit-ups and Sargent jumps showed a significant increase and other physical performance indicators such as the duration of sprinting and 9x4 running in the capsaicin supplement group in the post-test compared to the pre-test showed a significant decrease. In the inter-group comparison, only the fatigue index of creatine phosphokinase in the capsaicin supplement group showed a significant decrease compared to the placebo. Also, among the physical performance indicators, the number of pull-ups, sit-ups, and Sargent jumps in the supplement group showed a significant increase compared to the placebo and the duration of the 20-meter sprint showed a significant decrease. Based on the findings of this study, it appears that taking capsaicin supplements reduces fatigue in young girls and can have a positive effect on athletic performance.