Objective To investigate the mediation effects of positive coping style and self-esteem on the relationship between mental resilience and fatigue. Methods A total of 1 092 males were selected by cluster sampling, and were surveyed using multidimensional fatigue inventory scale, the Connor-Davidson resilience scale, simplified coping style questionnaire, and Rosenberg self-esteem scale. Pearson correlation analysis was used to explore the relationship between variables, and hierarchical linear regression was used to analyze the predictive value of mental resilience, positive coping style, and self-esteem for fatigue. Structural equation model was constructed to investigate the mediation roles of positive coping style and self-esteem in the relationship between mental resilience and fatigue. Results A total of 1 065 valid questionnaires were collected, with an effective rate of 97.53%. The results of Pearson correlation analysis suggested that fatigue was negatively associated with mental resilience, positive coping style, and self-esteem (r＝—0.619, —0.538, —0.589; all P＜0.01), and positively associated with negative coping style (r＝0.340, P＜0.01); mental resilience was positively correlated with positive coping style and self-esteem (r＝0.706, 0.583; both P＜0.01), but not correlated with negative coping style (r＝0.014, P＞0.05). Self-esteem was negatively correlated with negative coping style (r＝—0.181, P＜0.01), and positively correlated with positive coping style (r＝0.474, P＜0.01). The results of hierarchical linear regression showed that mental resilience could independently explain 38.3% of the variance of fatigue (P＜0.01), and self-esteem and positive coping style could explain an additional 9.2% variance of fatigue (P＜0.01). The model fit index of structural equation model was χ²＝31.404, df＝7, χ²/df＝4.486, with the comparative fit index being 0.994, Tucker-Lewis index being 0.998, and root mean square error of approximation being 0.014. The mediation effect analysis showed that the mediation effects of positive coping style (P＝0.01) and self-esteem (P＜0.001) were significant, with that of self-esteem being greater than that of positive coping style (P＝0.007), and the direct effects of mental resilience was significant (P＜0.001). Conclusion Self-esteem and positive coping style have partial mediation effect on the relationship between mental resilience and fatigue, and the mediation effect of self-esteem is greater, suggesting that mental resilience, self-esteem and positive coping style are protective factors of fatigue. Carrying out resilience training, improving self-esteem, and adopting positive coping style can reduce the fatigue.