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 center dot 8% reported at least one mental health disorder: 17 center dot 6% endorsed a mood disorder, 24 center dot 7% an anxiety disorder, 2 center dot 4% an eating disorder, and 11 center dot 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 < 0 center dot 05). Yet, Black Americans with SCD were not at greater odds of having a mental health disorder compared to those with other medical conditions. When compared to the group with no conditions, however, individuals with SCD had 2 center dot 57 greater odds of mood disorder (95% confidence interval: 1 center dot 43-4 center dot 65; P = 0 center dot 002). The effect remained when controlling for socioeconomic status, marital status, and perceived physical health. In this study, almost 40% of Black American adults with SCD presented with a mental health disorder. Prevalence of mental health disorders was similar among those with non-heritable medical conditions, but those without a medical condition had a lower prevalence than in SCD. Among Black Americans, there appear to be unmeasured factors, common across medical conditions, that are linked to mental health disorders.