Introduction: Because of their inability to access adequate medical care, transportation, and nutrition, socially vulnerable populations are at an increased risk of health challenges during disasters. This study estimates the association between case counts of COVID-19 infection and social vulnerability in the U.S., identifying counties at increased vulnerability to the pandemic. Methods: Using Social Vulnerability Index and COVID-19 case count data, an ordinary least squares regression model was fitted to assess the global relationship between COVID-19 case counts and social vulnerability. Local relationships were assessed using a geographically weighted regression model, which is effective in exploring spatial nonstationarity. Results: As of May 12, 2020, a total of 1,320,909 people had been diagnosed with COVID-19 in the U.S. Of the counties included in this study (91.5%, 2,844 of 3,108), the highest case count was recorded in Trousdale, Tennessee (16,525.22 per 100,000) and the lowest in Tehama, California (1.54 per 100,000). At the global level, overall Social Vulnerability Index (e b =1.65, p=0.03) and minority status and language (e b =6.69, p<0.001) were associated with increased COVID-19 case counts. However, on the basis of the local geographically weighted model, the association between social vulnerability and COVID-19 varied among counties. Overall, minority status and language, household composition and transportation, and housing and disability predicted COVID-19 infection. Conclusions: Large-scale disasters differentially affect the health of marginalized communities. In this study, minority status and language, household composition and transportation, and housing and disability predicted COVID-19 case counts in the U.S. Addressing the social factors that create poor health is essential to reducing inequities in the health impacts of disasters.