Persons of color in the US experience the worst COVID-related outcomes and account for the majority of COVID-19 cases and hospitalizations among healthcare workers. In a pandemic where minority populations and healthcare workers are among the hardest hit, nurses of color are undoubtedly taxed. Moreover, their workplace racism experiences represent a dual pandemic in that the effects of COVID-19 worries and workplace racism may synergize to the detriment of their emotional well-being. The purpose of this study was to examine the direct, indirect, and interactive effects of individual (race, COVID worry), interpersonal (workplace racial microaggressions), and institutional (racial climate) factors on hospital-based nurses’ emotional well-being. A sample of 788 registered nurses who worked in New Jersey hospitals completed an electronic survey. Compared to White nurses, nonwhite nurses reported higher emotional distress, more negative racial climates, more racial microaggressions, and higher levels of COVID worry. Nurses’ worry about getting sick from COVID and multiple racial microaggression experiences had the largest effects on the likelihood of high emotional distress. Racism variables and worry about COVID mediated indirect effects of nonwhite race on emotional distress. Racial microaggressions mediated an indirect effect of racial climate on this outcome. Nurses who were worried about getting sick from COVID and experienced multiple microaggressions and/or the most negative racial climates had severe emotional distress. There is a need for sustained investment in a racially diverse nursing workforce. Mitigating workplace racism in hospitals is crucial, particularly during public health crises that disproportionately threaten minority populations and healthcare workers.