No previous study has analyzed the impact of caffeine intake on prooxidant-antioxidant balance and muscle damage following resistance exercise. The aim of this study was to determine the effect of 3 mg/kg of caffeine on the number of repetitions and the prooxidant-antioxidant balance and muscle damage after a session of full-body resistance exercise. Ten resistance-trained men habituated to caffeine participated in a randomized, crossover and double-blind experiment. Each participant performed two identical resistance training sessions after the intake of 3 mg/kg of caffeine or a placebo. Blood was collected before and 60 min after substance intake, just after exercise, 60 minutes after exercise, and 24 hours after testing to evaluate the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase), non-enzymatic antioxidants (reduced glutathione, uric acid) levels of oxidative stress markers (plasma malondialdehyde) and muscle damage markers (creatine kinase, lactate dehydrogenase). There were no significant differences between placebo and caffeine conditions in the total number of repetitions (180 ± 15 vs 185 ± 14 repetitions, respectively; p = 0.276; Effect size [ES] = 0.34), the total time under tension (757 ± 71 vs 766 ± 56 s, respectively; p = 0.709; ES = 0.14) or the rating of perceived exertion (13.8 ± 2.7 vs 14.7 ± 2.7 a.u., respectively; p = 0.212; ES = 0.32). Reduced glutathione concentration obtained 1 hour after exercise was higher with caffeine than with placebo (p = 0.047), without significant difference between conditions for any other prooxidant-oxidant or muscle damage marker at any time point (p > 0.050 for all). The oral intake of 3 mg/kg of caffeine by resistance-trained men habituated to caffeine did not enhance the number of repetitions during a medium load full-body resistance training session to failure and had a minimal impact on the prooxidant-antioxidant balance and muscle damage. The study was registered prospectively at ClinicalTrials.gov with the following ID: NCT05230303.

• 3 mg/kg of caffeine did not enhance the number of repetitions during a full-body resistance training session in resistance-trained men habituated to caffeine.

• 3 mg/kg of caffeine had minimal impact on the prooxidant-antioxidant balance and muscle damage induced by the exercise.

• It is possible that caffeine may provide some benefits to reduce oxidative stress after a resistance exercise training session. Further experiments should investigate if these reduced oxidative stress with caffeine counteract some of the training adaptations induced by resistance exercise (f.eg. muscle hypertrophy).