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AbstractObjective:To characterize residential social vulnerability among healthcare personnel (HCP) and evaluate its association with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection.Design:Case–control study.Setting:This study analyzed data collected in May–December 2020 through sentinel and population-based surveillance in healthcare facilities in Colorado, Minnesota, New Mexico, New York, and Oregon.Participants:Data from 2,168 HCP (1,571 cases and 597 controls from the same facilities) were analyzed.Methods:HCP residential addresses were linked to the social vulnerability index (SVI) at the census tract level, which represents a ranking of community vulnerability to emergencies based on 15 US Census variables. The primary outcome was SARS-CoV-2 infection, confirmed by positive antigen or real-time reverse-transcriptase– polymerase chain reaction (RT-PCR) test on nasopharyngeal swab. Significant differences by SVI in participant characteristics were assessed using the Fisher exact test. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) for associations between case status and SVI, controlling for HCP role and patient care activities, were estimated using logistic regression.Results:Significantly higher proportions of certified nursing assistants (48.0%) and medical assistants (44.1%) resided in high SVI census tracts, compared to registered nurses (15.9%) and physicians (11.6%). HCP cases were more likely than controls to live in high SVI census tracts (aOR, 1.76; 95% CI, 1.37–2.26).Conclusions:These findings suggest that residing in more socially vulnerable census tracts may be associated with SARS-CoV-2 infection risk among HCP and that residential vulnerability differs by HCP role. Efforts to safeguard the US healthcare workforce and advance health equity should address the social determinants that drive racial, ethnic, and socioeconomic health disparities.