Abstract Objectives To identify determinants of mental health in healthcare workers (HCW) during the COVID-19 pandemic. Methods A cohort of Canadian HCW completed four questionnaires giving details of work with patients, ratings of workplace supports, a mental health questionnaire and substance use. Principal components were extracted from 23 rating scales. Risk factors were examined by Poisson regression. Results 4854 (97.8%) of 4964 participants completed ratings and mental health questionnaires. HCWs working with patients with COVID-19 had high anxiety and depression scores. One of three extracted components, ‘poor support’, was related to work with infected patients and to anxiety, depression and substance use. Availability of online support was associated with feelings of better support and less mental ill-health. Conclusions Work with infected patients and perceived poor workplace support were related to anxiety and depression during the pandemic.