Objective:To investigate the compassion fatigue of medical staff working in centralized quarantine sites and its influencing factors during the COVID-19 epidemic.Methods:From September 2020 to October 2020, a cross-sectional study was conducted on 213 medical staff working in 13 quarantine centers in two districts of Shanghai. A self-made general information questionnaire, professional quality of life scale, general self-efficacy scale and perceived social support scale were used in the study.Results:The score of empathy satisfaction was 33.00(28.25, 37.75), and there were 141 cases (66.20%) with supercritical value. The score of job burnout was 26.00(21.50, 30.50), and 96 cases (45.07%) exceeded the critical value. The score of secondary traumatic stress was 25.00(20.50, 29.50), and 192 cases (90.14%) exceeded the critical value. Multivariate logistic regression analysis showed that average daily working hours, job satisfaction, self-evaluation of work pressure, general self-efficacy and perceived social support were the influencing factors of compassion fatigue among medical staff. Compared with those who worked for 0 h in the polluted area, those who worked for more than 8 h had a higher degree of compassion fatigue ( OR=7.787, 95 %CI: 1.127-53.820);compared with those who were more satisfied with their work, those who were less satisfied with their work had a higher degree of compassion fatigue ( OR=6.209,95 %CI:1.474-26.157); compared with those with no or low stress, those with high stress had higher degree of compassion fatigue ( OR=2.567, 95 %CI: 1.228-5.366); compared with those with high self-confidence, those with low self-confidence or moderate self-confidence had higher degree of compassion fatigue ( OR=13.519, 95 %CI: 3.394-53.848; OR=3.462, 95 %CI: 1.038-11.548); compared with those with high perceived social support, those with low perceived social support had higher degree of compassion fatigue ( OR=2.071, 95 %CI: 1.027-4.175) (all P<0.05). Conclusion:The status of compassion fatigue of medical staff working in the centralized quarantine sites need to be improved. We should pay more attention to the those medical staff having long daily working hours in the polluted area, those with low job satisfaction, poor self-evaluation of work pressure, poor general self-efficacy and low perceived social support.