Background: Compassion fatigue, moral distress, and moral injury are interconnected phenomena that have a detrimental impact on the delivery of nursing care. Nurses possess the inherent resilience necessary to effectively handle these three adverse occurrences. Aim: To determine the mediating impact of resilience on compassion fatigue, moral distress, and moral injury among nurses in Saudi Arabia. Design: The final product was a structural equation model (SEM) generated using a quantitative correlation cross-sectional design, and we followed the STROBE guidelines for this study. Methods: The study involved a sample of 511 staff nurses, who were selected using consecutive sampling. The study was conducted in three government hospitals in Saudi Arabia. Ethical considerations: This study received approval from Ethics Committee under approval number H-2021-151 on March 5, 2021. The survey’s description and consent statements were clearly presented on Google survey forms in both English and Arabic. Results: Results showed that resilience negatively influenced moral distress, while compassion fatigue and moral injury had a positive influence. Likewise, compassion fatigue had a direct, positive effect on moral distress and moral injury, and moral distress had a direct, positive effect on moral injury. Analyses also showed that resilience had positive, indirect effects on moral injury through the mediation of both compassion fatigue and moral distress. Similarly, compassion fatigue had a positive, indirect effect on moral injury through the mediation of moral distress. Conclusion: Because resilience enables nurses to adapt, it helps them overcome obstacles in their career and professional lives. Resilience is frequently cited by nurses as a protective quality. Moral injury, compassion fatigue, and moral distress can negatively impact the health of nurses. Implications for the profession and/or patient care: Nurse leaders should develop programs and initiate efforts to improve nurses’ resilience as an important protective trait against compassion fatigue, moral distress, and moral injury. Patient or Public Contribution: There was no public or patient participation in this study.