The literature suggests that children and adolescents with sickle cell disease (SCD) are at risk of lower self-esteem than healthy peers. Research on factors predicting low self-esteem in children and adolescents with SCD is sparse, yet findings from studies of healthy children and adolescents indicate that age and sex are related to self-esteem. The primary aim of the current study was to examine the relationships between self-esteem in children and adolescents with SCD and age, sex, disease severity, and physical stature using data from, the Cooperative Study of Sickle Cell Disease. The study also examined whether age and sex moderated the relationship between physical stature and self-esteem. Results indicated that self-esteem scores and age were positively correlated, with scores dipping around the time of school transitions. Sex, disease severity, and physical stature were not predictive of self-esteem in children and adolescents with SCD in this study. Future research should focus on identifying and examining other possible factors that may be related to self-esteem in youth with SCD