BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has broken out and even spread globally. The healthcare system worldwide faces enormous challenges, and nurses are at the highest risk as one of the leading forces. It's worth paying attention to nurses' anxiety and job burnout. This study aimed to investigate nurses' levels of burnout and anxiety during the epidemic of COVID-19 and to analyze influencing factors of burnout. METHODS: A cross-sectional survey was conducted from 19 to 25 February 2020. Questionnaires such as the basic information questionnaire, Maslach Burnout Inventory-General Survey (MBI-GS), and State-Trait Anxiety Inventory (STAI) were used among 1011 nurses in Wuhan tertiary hospitals via the online survey. The final number of valid questionnaires was 885. The effective response rate was 87.5%. RESULTS: The average score of MBI-GS was 11.50, 6.02, 24.47, respectively. The average score for state anxiety was 45.52 and trait anxiety, 43.78. Anxiety was positively associated with emotional exhaustion and cynicism, and negatively related to personal accomplishment. The protective factors of burnout were personnel agency, five years or less work experience, living in hospital dormitory, Wuhan medical team, working time exceeding 9 h, and the best knowledge of COVID-19. The absence of siblings, median job title, working in isolation wards, three or more night shifts per week, living in hotels, and being surrounded by confirmed or suspected medical staff were all negative factors. CONCLUSIONS: Nurses had high anxiety levels during the COVID-19 period, but the level of burnout was mild to moderate. Managers should continue to pay attention to nurses' psychological state and related factors and intervene to stabilize the nursing team.