Our aim was to determine differences in the prevalence of mental health disorders between Black Americans living with sickle cell disease (SCD) and Black Americans with other, non-heritable medical conditions, or no medical conditions. We examined the prevalence of mental health disorders among a non-institutionalized, community sample of Black adults in the US from the National Survey of American Life. We compared the odds of mental health disorders between Black American adults with SCD and those with other medical conditions, or no medical condition. Among the SCD group, 38·8% reported at least one mental health disorder: 17·6% endorsed a mood disorder, 24·7% an anxiety disorder, 2·4% an eating disorder, and 11·8% a childhood disorder. Compared to those with other medical conditions, Black Americans with SCD had greater poverty, more children in the household, and were less likely to be married/cohabitating (all P