For Black children with sickle cell disease (SCD) and their families, high disease stigmatization and pervasive racism increase susceptibility to discrimination in healthcare settings. Childhood experiences of discrimination can result in medical nonadherence, mistrust of healthcare providers, and poorer health outcomes across the lifespan. Caregivers and medical providers are essential to childhood SCD management and are therefore well-positioned to provide insight into discrimination in the context of pediatric SCD. This mixed-methods study sought caregivers’ and providers’ perspectives on processes underlying discrimination and potential solutions to mitigate the negative effects of perceived discrimination among children with SCD. Caregivers (N = 27) of children with SCD (≤ 12 years old) and providers from their hematology clinics (N = 11) participated in individual semi-structured interviews exploring experiences of discrimination and daily SCD management and completed a quantitative measure of discrimination. Qualitative data were collected until themes reached saturation and subsequently transcribed verbatim, coded, and analyzed using applied thematic analysis. Quantitative and qualitative data converged to suggest the pervasiveness of discrimination in healthcare settings. Three qualitative themes emerged: (1) healthcare system factors underlie discrimination, (2) families’ challenging interactions with providers lead to perceptions of discrimination, and (3) experiences of discrimination impact caregiver-provider interactions. Both caregivers and providers highlighted building trusting patient-provider relationships and encouraging patients’ self-advocacy as means to reduce experiences and impacts of discrimination. These findings offer potential approaches to tangibly mitigate occurrences of discrimination in pediatric healthcare settings by trust building, accountability keeping, and fostering rapport to improve quality of care and pediatric SCD health outcomes.