Objectives:To describe the burden and sources of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP), such as occupational role, work setting, vaccination status, and patient contact between March 2020 through May 2022.Design:Active prospective surveillance.Setting:Large tertiary-care teaching institution with inpatient and ambulatory care services.Results:We identified 4,430 cases among HCPs between March 1, 2020, through May 31, 2022. The median age of this cohort was 37 years (range, 18–89); 2,840 (64.1%) were female; and 2,907 (65.6%) were white. Most of the infected HCP were in the general medicine department, followed by ancillary departments and support staff. Less than 10% of HCP SARS-CoV-2–positive cases worked on a COVID-19 unit. Of the reported SARS-CoV-2 exposures, 2,571 (58.0%) were from an unknown source, 1,185 (26.8%) were from a household source, 458 (10.3%) were from a community source, and 211 (4.8%) were healthcare exposures. A higher proportion of cases with reported healthcare exposures was vaccinated with only 1 or 2 doses, whereas a higher proportion of cases with reported household exposure was vaccinated and boosted, and a higher proportion of community cases with reported and unknown exposures were unvaccinated (P< .0001). HCP exposure to SARS-CoV-2 correlated with community-level transmission regardless of type of reported exposure.Conclusions:The healthcare setting was not an important source of perceived COVID-19 exposure among our HCPs. Most HCPs were not able to definitively identify the source of their COVID-19, followed by suspected household and community exposures. HCP with community or unknown exposure were more likely to be unvaccinated.