Individuals with a chronic illness such as sickle cell disease are at risk for depression. Moreover, they are at risk for untreated depression. Depression may go untreated because of the stigma and high rates of disability associated with this chronic illness that most often affects African Americans in the United States. The purpose of this cross-sectional study was to describe depressive symptoms using the Beck Depression Inventory Fast Screen in a sample of 232 African American adults with sickle cell disease. Respondents reported higher levels of depression (26%) and depressive symptoms (32%) than did the overall United States population (9.5%). All adults with chronic illnesses need to be screened for depression in primary care practice sites where the diagnosis and treatment of depression needs to be coordinated.