This chapter highlights the disproportionate burden experienced by racial and ethnic minorities in the US during the COVID-19 pandemic. Non-White populations in the U.S. make up 55 percent of all COVID-19 cases and about 40 percent of the total population. Mortality parallels the case rate with 33 percent to 53 percent increase in deaths compared to 11 percent among Whites. The underlying factors contributing to increased infection rates will be reviewed with emphasis on the proportion in essential work with less salaried employment with health benefits, and no option to telework. This is exacerbated by the more crowded housing with multiple generations and/or more than one family in a living unit. These factors lead to a decreased ability to implement physical distancing during daily routines, self-isolation at home or outdoor activity in isolation. The decrease access to broadband has further impaired schooling, work options and access to information. Other factors such as discrimination, healthcare access and utilization, economic stability, and others put racial and ethnic minority groups at increased risk of getting COVID-19. Once infected, a higher rate of underlying comorbidities, especially diabetes, has led to more severe manifestations and a resulting higher share of of mortality. Generalized mistrust in governmental institutions and health care system has been exacerbated by misinformation about the pandemic. The importance of working towards establishing a community-engaged approach that promotes trust in science through sustainable long-term partnerships is essential given the higher rate of vaccine hesitancy, especially in African Americans. Structural issues that perpetuate inequalities need to be addressed through policy and legal changes supported by research evidence.