Background: Egypt joined several countries in immunizing her citizens with COVID19 vaccines; a priority was given to health care workers (HCWs), then to patients with chronic diseases. However, HCWs are exposed to a higher viral load; in addition, asymptomatic infection is commoner among them, thus potentially exposing them to a more severe illness. Objective(s): To identify the determinants of the severity of COVID-19 infection among HCWs. Methods: A case control study was conducted, where we recruited HCWs diagnosed as moderate or severe COVID-19 from isolation and critical care units; and compared their vaccination exposure with that among matched controls. A data collection sheet was filled by residents and included information about mask wearing, comorbidities, smoking, and COVID-19 manifestations. Results: The predictors that significantly affected severity of infection were cardiovascular or cerebrovascular diseases, being a nurse, and mask compliance (OR 17.38 p=0.012 *, OR 5.86, p=0.002*, and OR=0.06, p=0.001 *respectively). Most females, as well as nurses were not vaccinated (90% p= 0.009 *, and 83.3% p=0.016 *respectively). There was no significant difference in mean oxygen saturation between vaccinated and non-vaccinated cases. Conclusion: Among HCWs, the most significantly protective factor against COVID-19 moderate and severe illness was mask compliance. Furthermore, being a nurse as well as having cardiovascular or cerebrovascular disease were significant positive predictors of getting a more severe disease. There was no significant effect of vaccination on severity of COVID19 illness.