Prior to the widespread use of vaccinations, healthcare workers (HCWs) faced the double burden of caring for unprecedented numbers of critically ill COVID-19 patients while also facing the risk of becoming infected themselves either in healthcare facilities or at home. In order to assess whether SARS-CoV-2-positivity rates in HCWs reflected or differed from those in their residential areas, we compared the SARS-CoV-2-positivity rates during 2020 among HCWs in Hadassah Hebrew University Medical Centers (HHUMC), a tertiary medical center in Jerusalem, Israel, to those of the general population in Jerusalem, stratified by neighborhood. Additionally, we compared the demographic and professional parameters in every group. Four percent of the adult population (>18 years) in Jerusalem tested positive for SARS-CoV-2 during 2020 (24,529/605,426) compared to 7.1% of HHUMC HCWs (317/4470), rate ratio 1.75 (95% CI 1.57–1.95), with wide variability (range 0.38–25.0) among different neighborhoods. Of the 30 neighborhoods with more than 50 infected HCWs, 25 showed a higher positivity rate for HCWs compared to the general population. The higher risk of HCWs compared to residents representing the general population in most neighborhoods in Jerusalem may be explained by their behavior in and out of the hospital.