PurposeHealthcare workers were recruited early in 2020 to chart effects on their health as the COVID-19 pandemic evolved. The aim was to identify modifiable workplace risk factors for infection and mental ill health.ParticipantsParticipants were recruited from four Canadian provinces, physicians (medical doctors, MDs) in Alberta, British Columbia, Ontario and Quebec, registered nurses (RNs), licensed practical nurses (LPNs) and healthcare aides (HCAs) in Alberta and personal support workers (PSWs) in Ontario. Volunteers gave blood for serology testing before and after vaccination. Cases with COVID-19 were matched with up to four referents in a nested case-referent study.Findings to dateOverall, 4964/5130 (97%) of those recruited joined the longitudinal cohort: 1442 MDs, 3136 RNs, 71 LPNs, 235 PSWs, 80 HCAs. Overall, 3812 (77%) were from Alberta. Prepandemic risk factors for mental ill health and respiratory illness differed markedly by occupation. Participants completed questionnaires at recruitment, fall 2020, spring 2021, spring 2022. By 2022, 4837 remained in the cohort (127 had retired, moved away or died), for a response rate of 89% (4299/4837). 4567/4964 (92%) received at least one vaccine shot: 2752/4567 (60%) gave postvaccine blood samples. Ease of accessing blood collection sites was a strong determinant of participation. Among 533 cases and 1697 referents recruited to the nested case-referent study, risk of infection at work decreased with widespread vaccination.Future plansSerology results (concentration of IgG) together with demographic data will be entered into the publicly accessible database compiled by the Canadian Immunology Task Force. Linkage with provincial administrative health databases will permit case validation, investigation of longer-term sequelae of infection and comparison with community controls. Analysis of the existing dataset will concentrate on effects on IgG of medical condition, medications and stage of pregnancy, and the role of occupational exposures and supports on mental health during the pandemic.