Objective To investigate the status and influencing factors of compassion fatigue among medical staff working in Fangcang shelter hospitals during the COVID-19 outbreak. Methods A total of 219 medical staffers working in 3 Fangcang shelter hospitals in Wuhan were investigated with the Professional Quality of Life Scale (ProQOL) and the Connor-Davidson Resilience Scale (CD-RISC). Results The scores of compassion fatigue among the medical staff working in Fangcang shelter hospitals were as follows: sympathy satisfaction (38.74±7.83), occupational burnout (21.64±5.05) and secondary trauma stress (20.90±6.29). Among them, 105 (47.95%) had mild compassion fatigue, 32 (14.61%) moderate, and 23 (10.50%) severe. The level of compassion fatigue was affected by the provinces where the medical staffers were from, work experience of public health emergencies, length of service in Fangcang shelter hospitals, adaptability to the working environment, workload, sleep and psychological resilience （P<0.05，P<0.01）. Conclusion Under COVID-19 outbreak, medical staff shared a commom condition of compassion fatigue. Meausres should be taken to ramp up training and supervision related to public health emergencies, optimize human resource management, creat a good working atmosphere, and implement humanistic care to frontline medical staff, etc., in an effort to improve the state of compassion fatigue in medical staff, and protect their physical and mental well-being.