Reduced growth and delayed maturation have been described in children with sickle cell disease (SCD). This study investigated growth and hemolysis in children with SCD in the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) cohort. The database includes 5287 children, of which, 3305 had at least 2 growth measurements over a 5-year period. Body mass index was converted to z-scores (zBMI), and 19.8%, 66.1%, 14.2% of children were classified as underweight, normal, and overweight/obese, respectively. Multivariable analysis of growth was conducted and included variables: Age, sex, blood pressure, hemoglobin, reticulocyte count, treatment with chronic red cell transfusion therapy (CRCT), or hydroxyurea therapy. Baseline hemoglobin levels were associated with the lower odds of being underweight (odds ratio [OR]=0.93, 95% confidence interval [CI]: 0.86-0.99), and higher odds of being overweight/obese (OR: 1.26, 95% CI: 1.17-1.36) compared with normal zBMI. CRCT was associated with being overweight/obese at baseline (OR: 1.85, 95% CI: 1.31-2.60). Overall, results showed that children who were underweight improved regardless of therapy over the 2-year time period. However, children on CRCT are at higher risk for being overweight and should be monitored closely.