Health care workers (HCWs) experienced greater risk of SARS-CoV-2 infection during the COVID-19 pandemic. This study applies a cost-of-illness (COI) approach to model the economic burden associated with SARS-CoV-2 infections among HCWs in five low- and middle-income sites (Kenya, Eswatini, Colombia, KwaZulu-Natal province, and Western Cape province of South Africa) during the first year of the pandemic. We find that not only did HCWs have a higher incidence of COVID-19 than the general population, but in all sites except Colombia, viral transmission from infected HCWs to close contacts resulted in substantial secondary SARS-CoV-2 infection and death. Disruption in health services as a result of HCW illness affected maternal and child deaths dramatically. Total economic losses attributable to SARS-CoV-2 infection among HCWs as a share of total health expenditure ranged from 1.51% in Colombia to 8.38% in Western Cape province, South Africa. This economic burden to society highlights the importance of adequate infection prevention and control measures to minimize the risk of SARS-CoV-2 infection in HCWs.