To explore and determine relationship between psychosocial factors and work-related fatigue among emergency and critical care nurses in Brunei.Cross-sectional study conducted on all emergency and critical care nurses across Brunei public hospitals from February to April 2016.201 nurses participated in the study (82% response rate). A total of 36% of the variance of chronic fatigue was explained by stress, trust in management, decision latitude, self-rated health, and work-family conflict. Burnout, self-rated health, commitment to workplace, and trust in management explained 30% of the variance of acute fatigue. Stress, work-family conflict and reward explained 28% of the variance of intershift recovery after controlling for significant sociodemographic variables. Smoking was identified as an important sociodemographic factor for work-related fatigue.Psychosocial factors were good predictors of work-related fatigue. A range of psychosocial factors were established, however more research is required to determine all possible causation factors of nurses' work-related fatigue.