Abstract Background This study explores trends and work-related determinants of mental health and wellbeing among health and care workers in Europe since the COVID-19 pandemic. The aim is to determine where investments can best be made to protect and support mental health and wellbeing among health and care workers to improve retention and recruitment. Methods Data are analysed from the National Health Service staff survey in England and the Health Service Executive ‘Your Opinion Counts’ survey in Ireland to explore trends in mental health and wellbeing and burnout. Evidence is then taken from a series of European Observatory policy briefs, based on expert-led literature reviews, to explore determinants of poor mental health and wellbeing and to identify potential areas for investment. Results Rates of burnout and poor mental health and wellbeing have increased in England and Ireland since the start of the pandemic among all professional groups. Workplace-based factors are important determinants of poor mental health and wellbeing, and can be grouped into: macro-level structural factors such as staff shortages, poor working conditions and low pay; meso-level organisational factors including poor leadership, and insufficient education, training and support; micro-level individual factors such as insufficient self-care or not seeking support. However, determinants at the micro-level, especially seeking support from others, are largely shaped by structural or organisational factors. Conclusions Increased financing to address structural and organisational determinants of mental health and wellbeing contributes to improved patient care, better staff experience, lower rates of absenteeism, and enhanced recruitment and retention. It is therefore one of the best health system investments that can be made.