Anxiety and depression are well documented complications of adjustment in sickle cell disease (SCD), but psychosis as a direct complication of or adjustment in SCD is uncommon. This article reports a case of psychosis in an adolescent with SCD. It advocates for further study on the relationship between psychosis and brain tissue silent-infarcts in these patients and the urge for alertness on the part of health care professionals regarding a holistic approach to the management of these children and adolescents with SCD.