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Background: Despite past and ongoing efforts to achieve health equity in the USA, racial and ethnic disparities persist and appear to be exacerbated by COVID-19. Objective: Evaluate neighborhood-level deprivation and English language proficiency effect on disproportionate outcomes seen in racial and ethnic minorities diagnosed with COVID-19. Design: Retrospective cohort study Setting: Health records of 12 Midwest hospitals and 60 clinics in Minnesota between March 4, 2020, and August 19, 2020 Patients: Polymerase chain reaction–positive COVID-19 patients Exposures: Area Deprivation Index (ADI) and primary language Main Measures: The primary outcome was COVID-19 severity, using hospitalization within 45 days of diagnosis as a marker of severity. Logistic and competing-risk regression models assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race, effects of ADI and primary language were measured using logistic regression. Results: A total of 5577 individuals infected with SARS-CoV-2 were included; 866 (n = 15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 vs. 40.4 years, p < 0.001) and more likely to be male (n = 425 [49.1%] vs. 2049 [43.5%], p = 0.002). Of those requiring hospitalization, 43.9% (n = 381), 19.9% (n = 172), 18.6% (n = 161), and 11.8% (n = 102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity: Hispanic patients (OR 3.8, 95% CI 2.72–5.30), Asians (OR 2.39, 95% CI 1.74–3.29), and Blacks (OR 1.50, 95% CI 1.15–1.94). ADI was not associated with hospitalization. Non-English-speaking (OR 1.91, 95% CI 1.51–2.43) significantly increased odds of hospital admission across and within minority groups. Conclusions: Minority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes. Non-English-speaking accounts for differences across and within minority populations. These results support the ongoing need to determine the mechanisms that contribute to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity among minority groups. [ABSTRACT FROM AUTHOR]