Objective To investigate the current state of compassion fatigue among operating room nurses, analyze the factors influencing compassion fatigue (particularly psychological resilience), and provide a basis for developing a compassion fatigue intervention program for operating room nursing managers. Methods This cross-sectional study was conducted in February 2022. A total of 258 operating room nurses were surveyed using the Professional Quality of Life (ProQOL) scale and the Resilience Scale for Adults (RSA). The ProQOL demonstrated internal consistency reliability, with Cronbach's alpha values ranging from 0.75 to 0.88 across its three subscales. The Cronbach's alpha coefficient for the RSA was 0.91. Results Scores on various dimensions of compassion fatigue among operating room nurses were as follows: the total score was 84.07 (standard deviation [SD] = 7.74), with a mean score of 28.02. 92 nurses (35.5%) had no compassion fatigue or only mild compassion fatigue, whereas 166 nurses (64.3%) experienced moderate or greater compassion fatigue. The total score for psychological resilience was 112.9 (SD = 6.47), with a mean score of 18.82. Factors influencing compassion fatigue included the relationship between labor and personnel, the number of night shifts per week, and mental resilience. The differences were statistically significant (P < 0.05). Conclusion Compassion fatigue among nurses in the operating room is severe and is mainly influenced by factors such as night shift work, the relationship between labor and personnel, and mental resilience. Appropriate interventions are recommended to address these factors and reduce nurses' compassion fatigue. Clinical trial numberNot applicable.