Objective To explore the incidence of post-stroke fatigue and the related psychosocial factors, so as to lay a theoretical foundation for its prevention and treatment. Methods A total of 408 patients with stroke were investigated and analyzed by using the General Questionnaire, Fatigue Severity Scale (FSS), Self-rating Depression Scale( SDS), Mini-Mental State Examination( MMSE), Simplified Coping Style Questionnaire( SCSQ), Family Care Index Together( APGAR) and Social Support Revalued Scale( SSRS). Results The incidence of post-stroke fatigue among the 408 stroke patients was 64.5%. Single factor analysis showed that age, marital status, education, family function, depression, cognitive function, coping style and social support were related to post-stroke fatigue( P < 0.05). Multiple factors regression analysis showed that family function( OR=3.205,P=0.027), depression(OR=0.200,P=0.001), negative coping( OR=0.106,P=0.006) and objective support( OR=2.312,P=0.003) were predictors of post-stroke fatigue with statistical significance. Conclusions The incidence of post-stroke fatigue is high, good family function and more objective support can be used as protective factors for post-stroke fatigue. Depression and negative coping were risk factors for poststroke fatigue