Acute and chronic pain is a common hallmark of sickle cell disease (SCD) in children and adolescents, which can have a profound effect on their quality of life (QOL). However, this relationship is not well quantified. The purpose of this quantitative study was to examine the relationship between SCD pain burden and QOL among Black children ages 8-17 in Mississippi with SCD. The secondary aim was to compare children and caregiver reports of SCD pain burden and QOL with SCD. The social ecological model was used to identify personal factors that influence SCD pain burden and QOL of children with SCD. Eighty-five children and caregiver pairs completed paper surveys on demographics, pain burden, and QOL. Hierarchical linear regression results indicated that increased child SCD pain burden was statistically associated with decreased child's QOL (P