Background: We aimed to assess the personal and professional quality of life changes among health care workers of different professions during the COVID-19 pandemic in a large French university hospital. Other published data originated from countries with different health care systems and outbreak dynamics. Methods: All health care workers from our hospital were invited to fill-in an anonymous e-questionnaire of 71 questions regarding perceived personal, professional and overall quality of life before and during the first COVID-19 wave, general profile, occupation and job characteristics, change of assignment, COVID-care features if relevant, general perception during the first wave, and personal experience of being encouraged or stigmatised. Results: There were 794 participants, with a majority of nursing professionals (n = 416, 56%), including 57 nurse managers, 243 nurses, and 116 nurse assistants. Other participants were physicians (n = 188) and other health care staff (n = 140). Before the crisis, professional quality of life was low (6.5 on a 10-point scale) overall. The personal quality of life was higher (8.1) particularly for physicians and nurse managers. The COVID crisis saw a marked decrease in the personal quality of life (− 1.7), more pronounced in younger health care workers. Professional quality of life was less affected (− 0.4) and stayed almost constant for physicians. Staff in COVID units had a more positive perception of the crisis but experienced more fatigue, which resulted in similar quality of life levels in COVID and non-COVID units. Encouragements originated more often from relatives or colleagues than hospital managers and were exceptionally common: 63.4% of all participants, from 50.5% for other staff to 71.3% for physicians (p = 0.0005). Stigmatisation was reported by 19.3% of participants, with a higher proportion (p = 0.0001) among nurses (26.3%) and assistant nurses (23.3%) than among physicians (8.5%). From multivariate analysis, higher age, working as a physician and receiving encouragements were independently associated with lower loss of overall quality of life. Conclusions: The resilience of health care workers was high overall during the first COVID wave although the quality of life decreased more among nursing staff. Social support in the form of encouragements is a key part of management, particularly in times of crisis.