Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.