The risk of adjustment problems increases when a child has a serious life-threatening illness. This article estimates the frequency of adjustment problems across multiple domains for children and adolescents with sickle cell anemia (SCA). Parents provided information on the social, emotional, academic, and family adjustment of 327 children with SCA who were being treated at a comprehensive sickle cell clinic serving a predominantly poor and urban population. More than 25 percent of these children had emotional adjustment problems in the form of internalizing symptoms such as anxiety and depression. In addition, at least one child in five had problems related to social functioning and academic performance. These impairments were related significantly to the frequency of serious pain episodes but not to absolute family income. No significant differences in the data were found based on family income. The data also showed that the disruptive effects of the illness were related to gender and age.