ObjectiveThis study aimed to assess the association between perceived social support (PSS) and fatigue and the roles of hope, optimism, general self-efficacy and resilience as mediators or moderators on PSS-fatigue association among Rheumatoid Arthritis (RA) patients in China.MethodsA multi-center, cross-sectional study was conducted withinpatients diagnosed with RA in northeast China, in which 305 eligible inpatients were enrolled. The Multidimensional Fatigue Inventory, Multidimensional Scale of Perceived Social Support, Herth Hope Index, Life Orientation Test Revised, General Self-Efficacy Scale and Ego-Resiliency Scale were completed. The associations of PSS, hope, optimism, general self-efficacy and resilience with fatigue and the moderating roles of these positive psychological constructs were tested by hierarchical linear regression. Asymptotic and resampling strategies were utilized to assess the mediating roles of hope, optimism, general self-efficacy and resilience.ResultsThe mean score of the MFI was 57.88 (SD = 9.50). PSS, hope, optimism and resilience were negatively associated with RA-related fatigue, whereas DAS28-CRP was positively associated. Only resilience positively moderated the PSS-fatigue association (B = 0.03, β = 0.13, P<0.01). Hope, optimism and resilience may act as partial mediators in the association between PSS and fatigue symptoms (hope: a*b = -0.16, BCa 95%CI: -0.27, -0.03; optimism: a*b = -0.20, BCa 95%CI: -0.30, -0.10; resilience: a*b = -0.12, BCa 95%CI: -0.21–0.04).ConclusionsFatigue is a severe symptom among RA patients. Resilience may positively moderate the PSS-fatigue association. Hope, optimism and resilience may act as partial mediators in the association. PSS, hope, optimism and resilience may contribute as effective recourses to alleviate fatigue, upon which PSS probably has the greatest effect.