Background and Methods: The study was performed to investigate the demographic factors impacting COVID-19 cases in Virginia Zip Code Tabulation Areas [VZCTA] in 5 of the Virginia’s health planning regions (VHPRs). The data was collected from the Virginia Department of Health (VDH), spanning 5/15/2020-8/6/2020 (3 months) during the state’s first COVID-19 peak. Kruskal-Wallis with Bonferroni correction was used to compare the distribution of COVID-19 cases and demographic factors between the VHPRs. Pearson correlation was employed to determine correlations between COVID-19 Cases and demographic factors in VZCTA and VHPRs. Results: Incidence of COVID-19 was the highest in the suburban Northern region and the lowest in the rural-predominant southwestern region, 1017 vs. 420 per 100K population (p <0.05) (Table 1 for details). Overall state-wide and in almost all the VHPRs, the VZCTA with predominantly Hispanic and Black populations and high PCR testing rate were strongly associated with COVID-19 incidence in the univariate analyses. Interestingly, the younger age and household crowding (> 1.5 occupants/ room) were also associated with higher COVID-19 cases state-wide and in the Northern VHPR in the univariate analyses. In the multivariate analyses, Hispanic and Black populations were strongly associated with a higher COVID-19 incidence, especially in the Northern region. Considering demographic factors alone, ethnicity, median household income, and household crowding were the most important predictor of the COVID-19 incidence in Virginia ZCTA communities in multivariate analyses with a few important regional differences. The multivariate model’s R-value is 0.819 in the Northern region. Conclusions: The study highlights ethnicity as an essential social vulnerability in the contraction of COVID-19, which is also modified by the other factors in a regional manner accounting for the disparity in COVID-19 incidence across VHPRs. The information can guide critical public health decisions, e.g. vaccine distribution or implementation of critical health policies based on the social vulnerability in smaller population units - ZCTAs. As Virginia represents the average U.S. population concerning overall health and COVID-19 cases, the findings are likely to be generalizable to the U.S. population at large.