Objective To explore the relationship among fatigue, mental resilience, social support and self-efficacy in military personnel. Methods A total of 812 military personnel were tested with multidimensional fatigue inventory scale, the Connor-Davidson resilience scale, general self-efficacy scale, and Chinese version social support revalued scale. Pearson correlation analysis was used to explore the relationship between variables, and hierarchical linear regression was used to analyze the predictive effects of mental resilience, social support, and self-efficacy on fatigue. Structural equation model was constructed to investigate the mediation roles of social support and self-efficacy in the relationship between mental resilience and fatigue. Results A total of 794 valid questionnaires were collected, with an effective rate of 97.78%. The results of Pearson correlation analysis suggested that fatigue was negatively associated with mental resilience, social support, and self-efficacy (r=-0.646, -0.460, -0.520, all P<0.01), mental resilience was positively associated with social support and self-efficacy (r=0.458, 0.618, both P<0.01), and social support was positively associated with self-efficacy (r=0.423, P<0.01). Hierarchical linear regression analysis revealed that mental resilience could independently predict fatigue (P<0.01); social support and self-efficacy had a significant regression with fatigue (both P<0.01); and the 3 variables could explain 46.6% variance of fatigue. The results of structural equation model showed that social support and self-efficacy mediated the relationship between mental resilience and fatigue (P<0.001, P=0.026); furthermore, the chain mediation of social support and self-efficacy also played a mediation role in the relationship between mental resilience and fatigue (P<0.001). Conclusion The programs to enhance mental resilience, social support and self-efficacy can provide significant benefit for improving the abilities of military personnel to deal with fatigue and for improving their operational efficiency.