Severe obesity increases the risk for negative outcomes in patients with coronavirus disease 2019 (COVID-19). Our objectives were to investigate the effect of BMI on in-hospital outcomes in our New York City Health and Hospitals’ ethnically diverse population, further explore this effect by age, sex, race/ethnicity, and timing of admission, and, given the relationship between COVID-19 and hyperinflammation, assess the concentrations of markers of systemic inflammation in different BMI groups. A retrospective study was conducted in hospitalized patients with COVID-19 in the public health care system of New York City from 1 March 2020 to 31 October 2020. A total of 8833 patients were included in this analysis (women: 3593, median age: 62 years). The median body mass index (BMI) was 27.9 kg/m². Both overweight and obesity were independently associated with in-hospital death. The association of overweight and obesity with death appeared to be stronger in men, younger patients, and individuals of Hispanic ethnicity. We did not observe higher concentrations of inflammatory markers in patients with obesity as compared to those without obesity. In conclusion, overweight and obesity were independently associated with in-hospital death. Obesity was not associated with higher concentrations of inflammatory markers.