Little evidence estimated the exposure of psychosocial work stressors, work-related fatigue, and musculoskeletal disorders for nurses working in South-East Asian region, and research on this subject is almost nonexistent in Brunei. The main aim of our study was to provide a comprehensive exploration and estimate exposure of the study variables amongst emergency (ER) and critical care (CC) nurses in Brunei. The study also aims to compare whether experiences of ER nurses differ from those of CC nurses.This cross-sectional study was implemented in the ER and CC departments across Brunei public hospitals from February to April 2016 by using Copenhagen Psychosocial Questionnaire II, Occupational Fatigue Exhaustion Recovery scale, and Cornell Musculoskeletal Discomfort Questionnaire.In total, 201 ER and CC nurses (82.0% response rate) participated in the study. Quantitative demands of CC nurses were significantly higher than ER nurses. Even so, ER nurses were 4.0 times more likely [95% confidence interval (2.21, 7.35)] to experience threats of violence, and 2.8 times more likely [95% confidence interval: (1.50, 5.29)] to experience chronic fatigue. The results revealed that nurses experienced high quantitative demands, work pace, stress, and burnout. High prevalence of chronic and persistent fatigue, threats of violence and bullying, and musculoskeletal pain at the neck, shoulder, upper and lower back, and foot region, was also reported.This study has provided good estimates for the exposure rate of psychosocial work stressors, work-related fatigue, and musculoskeletal disorders among nurses in Brunei. It provided important initial insight for nursing management and policymakers to make informed decisions on current and future planning to provide nurses with a conducive work environment.