OBJECTIVE:To longitudinally assess the relationship of behavioral problems, intellectual functioning, and family functioning in children with sickle cell disease (SCD). METHOD:The study sample included 222 children enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD). The study protocol included intellectual evaluation and brain magnetic resonance imaging (MRI) of the children, and mothers completed the Child Behavior Checklist and Family Environment Scale. At least two complete sets of measures were obtained across four assessment points over the study period of 9 years. RESULTS:Intellectual functioning declined, but family functioning and behavior problem scores did not change significantly. Consistent behavior problems were reported by mothers for 9% of the children. The risk of consistent behavior problems was not related to MRI classification, gender, education level of mother, or age of the child but significantly increased with higher baseline levels of family conflict and decreased with higher baseline full-scale IQ. An increase in behavior problems was associated with an increase in family conflict. CONCLUSIONS:Maternal appraisal of family conflict is a risk factor for the small subgroup of children with SCD with consistent mother-reported behavior problems and a salient intervention target for fostering adaptation.