In the United States, COVID-19 has disproportionately affected Black persons. Sickle cell disease (SCD) and sickle cell trait (SCT) are genetic conditions that occur predominantly among Black individuals. It is unknown if individuals with SCD/SCT are at higher risk of severe COVID-19 illness compared with Black individuals who do not have SCD/SCT. The objective of our study was to compare COVID-19 outcomes, including the disease manifestations, hospitalization, and death, among individuals with SCD/SCT vs Black individuals who do not have SCD/SCT. We leveraged electronic health record data from a multisite research network to identify Black patients with COVID-19 who have SCD/SCT and those who do not have SCD/SCT. During the study period of 20 January 2020 to 20 September 2020, there were 312 patients with COVID-19 and SCD and 449 patients with COVID-19 and SCT. There were 45 517 Black persons who were diagnosed with COVID-19 but who did not have SCD/SCT. After 1:1 propensity score matching (based on age, sex, and other preexisting comorbidities), patients with COVID-19 and SCD remained at a higher risk of hospitalization (relative risk [RR], 2.0; 95% CI, 1.5-2.7) and development of pneumonia (RR, 2.4; 95% CI, 1.6-3.4) and pain (RR, 3.4; 95% CI, 2.5-4.8) compared with Black persons without SCD/SCT. The case fatality rates for those with SCD compared with Black persons without SCD/SCT were not significantly different. There also were no significant differences in COVID-19 outcomes between individuals with SCT and Black persons without SCD/SCT within the matched cohorts.