OBJECTIVE To evaluate the mental health status, stressors and self-adjustment of nurses in isolation wards at different periods in Wuhan, China. BACKGROUND Mental health issues easily occurred among the frontline medical workers of a major epidemic. However, the stressors and psychological adjustments experienced by nurses have not been well described. This is crucial to improving clinical quality and nursing safety and ensuring nurses' physical and psychological health. METHODS We performed a cross-sectional prospective study using the Self Reporting Questionnaire-20, stressor and self-adjustment questionnaire administered to frontline nurses in Wuhan at two time points: after they had worked in isolation wards for 7-10 days (T1 ) and 2 months (T2 ). This paper complies with the STROBE reporting guideline for cross-sectional studies. RESULTS T1 has 92 respondents, and T2 has 86. The positive rates of mental health problems were 26.09% and 9.30%, respectively, showing significantly different in the two periods. The main factors influenced mental health were self-perceived stress and only child status. The most common stressors were as follows: a large infected population, high infectivity; concerned about family's health status; high mortality if not treated in time (T1 ); and long duration of the epidemic, separate from family for a long time (T2 ). In terms of self-adjustment, 97.83%(T1 )/88.04%(T2 ) of nurses thought it was necessary, but 9(T1 ) /5(T2 ) chose to avoid addressing it, and 8(T1 ) /5(T2 ) utilised a professional psychological counselling hotline. CONCLUSIONS Mental health problems among frontline nurses fighting COVID-19 need special attention, so administrators should offer timely counselling and strengthen effective psychosocial support to improve their mental resilience. CONCLUSIONS This study surveyed the mental problems and self-adjustment status among nurses working Wuhan during the outbreak of COVID-19, to provide administrators with a scientific basis to effectively intervene.