Background: Heavy workload, job stress and lack of colleague support can lead to loneliness and burnout in nurses. Caring for a patient with constant pain can cause compassion fatigue. Loneliness at work and compassion fatigue also negatively affect the quality of patient care. Aim: This study aims to determine the effect of resilience on loneliness at work and compassion fatigue in nurses. Method: This is a descriptive cross-sectional study. The study was conducted with a total of 214 nurses. Results: A statistically significant negative relationship was found between the level of loneliness at work and resilience, and between resilience and compassion fatigue in nurses. The mediating role of resilience was found to be significant in the effect of loneliness at work on compassion fatigue in nurses. Conclusions: The results of this study suggest empowering nurses who have loneliness at work and compassion fatigue. Compassion fatigue is seen as occupational deformation. Nurses need to learn how to manage compassion fatigue, develop coping skills and receive support to ensure job satisfaction. In addition, nurse managers should create a reasonable workload for nurses. These efforts can increase the job satisfaction and patient care quality of nursing departments.