Moral courage is the ability to defend and practice ethical and moral action when faced with a challenge, even if it means rejecting pressure to act otherwise. However, moral courage remains an unexplored concept among middle eastern nurses. This study investigated the mediating role of moral courage in the relationship between burnout, professional competence, and compassion fatigue among Saudi Arabian nurses. Correlational, cross-sectional design following the STROBE guidelines. Convenience sampling was used to recruit nurses (n = 684) for four government hospitals in Saudi Arabia. Four validated self-report questionnaires (Nurses' Moral Courage Scale, Nurse Professional Competence Scale-Short Form, Maslach Burnout Inventory, and Nurses Compassion Fatigue Inventory) were used to collect data between May to September 2022. Spearman rho and structural equation modeling analyses were employed to analyze the data. The ethics review committee of a government university in Ha'il region, Saudi Arabia, approval this study (Protocol no.: H-2021-012; Approved: 08/022,021). Participants were fully explained the study aims, and consent was voluntarily secured. The emerging model showed that burnout had a direct and positive influence on compassion fatigue, while professional competence had a direct, negative effect on compassion fatigue. Moral courage had a small and direct but negative influence on compassion fatigue. Mediation analyses also indicated that moral courage significantly mediated the indirect effects of burnout and professional competence on compassion fatigue. Moral courage can be a crucial aspect in preserving the psychological and mental health of nurses, particularly under stressful conditions. Therefore, it is advantageous from an organizational and leadership standpoint to implement measures such as programs and interventions to foster moral courage among nurses.