Patients and families affected by various medical conditions report experiencing health-related stigma, which contributes to detrimental physical, psychological, and social outcomes. Sickle cell disease (SCD) is a genetic disorder that affects 89,000 individuals in the United States and is often associated with negative stereotypes and incorrect assumptions. The present study explored the perception of stigma as reported by caregivers of adolescents with SCD. Focus groups were conducted with 20 caregivers of patients with SCD. Focus groups were audio recorded and transcribed. The data were coded independently by two authors, and then reviewed conjointly until consensus was reached. Caregivers reported the perception of stigma in academic, medical, community, and family settings. They also reported internalized stigma including negative feelings toward having a child with SCD, feeling upset with others, and seeing negative emotions in their child due to SCD. Caregivers reported a general lack of knowledge about SCD across settings. These results demonstrated that stigma may affect individuals with SCD across multiple settings. These results also highlighted areas for intervention, with a focus on increasing communication and education toward medical providers, schools, and communities. Interventions can utilize technology, social media, and advertisement campaigns. Additionally, support groups for patients with SCD may help decrease stigma and validate patients' experiences.