INTRODUCTION: In humans, exercise-induced muscle damage often arise following eccentric contractions. While existing animal literature consistently demonstrates that females tend to experience less damage than males, findings from human studies present a contrasting picture. Some studies suggest no discernible difference between men and women, while others propose that men may be more susceptible to exercise-induced muscle damage than women. This study aimed to investigate whether muscle mass and strength could potentially account for any observed differences between men and women in the context of exercise-induced muscle damage. METHODS: Seventy-one men (mean ± SD; age: 24.5±4.8 years; height: 180.5±7.1 cm; body mass: 79.9±13.7 kg) and forty-eight women (mean ± SD; age: 23.5±3.9 years; height: 165.1±6.0 m; body mass: 63.3±9.8 kg) were recruited. After a force—velocity profile assessment (one leg press exercise), individual maximal isometric strength (F0) was determined. Subjects performed on a separate day 8 sets of ten 5-second eccentric repetitions at 85% of their individual F0. Before and after exercise (+0h, +24h, +48h, and +72h), the maximal isometric strength, muscle soreness, and creatine phosphokinase (CPK) levels of each participant were assessed. RESULTS: Maximal isometric strength significantly decreases after exercise and 24h after for men and women. Muscle soreness was affected by the time but not by the sex. Significant time effect was found in all the group between resting CPK levels and CPK levels at +0h (x1.22, p<0.01), +24h (x1.84, p<0.001), and +48h (x1.39, p<0.001). An effect of sex was observed on absolute CPK levels at all time point (p<0.001): men have greater CPK levels values compared to women. When CPK levels were normalized to the participant’s maximal strength and mass, no significant difference was observed between the sexes. CONCLUSION: Our results showed that the muscle damage differences observed between men and women after an eccentric exercise (absolute CPK values) were not significant when data were normalized to both mass and maximal strength. Differences in CPK level seem explained by the higher muscle mass and muscle strength engaged by the men during the exercise and not by the sex. However, the sex appears to impact the recovery of the initial strength level.