Objective To investigate the physical and mental condition and medicine consumption of medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019 (COVID-19). Methods A total of 144 frontline medical staff who fighting against the COVID-19 epidemic from a tertiary first-class hospital from Apr. 4 to May 12, 2022 were surveyed by questionnaires online. Their physical condition including body weight change before the medical work and one month later, sleep quality and the medicine consumption during the medical work were collected and analyzed. Results The mean body weight of frontline doctors before the medical work and one month later were (69.80±8.35) kg and (68.60±7.37) kg, while those of nurses were (55.36±8.27) kg and (53.80±7.38) kg, both showing a decreasing trend but without significant difference (all P>0.05). A total of 63.89% (92/144) frontline medical staff suffered from insomnia, of which 27.08% (39/144) needed drug intervention. The top 5 common diseases among frontline medical staff were sleep disorder (63.89%, 92/144), skin injury (25.69%, 37/144), body pain (23.61%, 34/144), oral ulcer (13.19%, 19/144), and acute upper respiratory tract infection (9.72%, 14/144). A total of 155 medical staff used drugs, and the top 5 common drugs were skin application (16.77%, 26/155), Ganmao'an granule (12.26%, 19/155), zolpidem tartrate tablets (11.61%, 18/155), Kangfuxin liquid (11.61%, 18/155), and celecoxib capsules (8.39%, 13/155). Conclusion Frontline medical staff in shelter hospitals are prone to have body weight change, sleep disorder, skin injury, body pain, oral ulcer, acute upper respiratory tract infection and so on, which suggests that in future similar large-scale medical support, it is necessary to pay sufficient attention to the physical condition of frontline medical staff and provide them sufficient medicine.