This research examined the emotional, social, and behavioral functioning of children with sickle cell disease (SCD) and classroom comparison peers from the perspective of primary and secondary caregivers. It was hypothesized that children with SCD would have more internalizing (emotional) and social problems and fewer externalizing (behavioral) problems than comparison peers. Caregivers of 70 children with SCD and 67 comparison peers completed the Child Behavior Checklist (CBCL) during visits to the children's homes. Relative to comparison peers, children with SCD were perceived by primary caregivers as having more total and internalizing problems and less total competence. Additionally, significantly more children with SCD exceeded clinical cutoffs on the CBCL. While caregivers of children with SCD perceive these children to be at a slightly elevated risk for problems across multiple domains, a significant number of children with SCD have problems in the clinical range. The authors recommend that vigorous screening programs for mental health problems should be included in the routine care of children with SCD, and programs of psychosocial intervention research should be implemented to ameliorate problems for the children at greatest risk.