|Sickle cell disease (SCD) is a complex group of genetic blood disorders that currently affects 90,000-100,000 Americans primarily of African descent. SCD leads to physiological and psychosocial distress. In relation to school, youth with SCD are at high risk of poor academic outcomes, including: low scores on tests of academic achievement, and increased risk of poor grades, special education, and grade retention. There is a paucity of literature on family functioning's effect on academic functioning in youth with SCD. Poor family functioning in youth with SCD has been related to many other psychosocial outcomes, such as behavior problems, poor mental health and quality of life. The current study examined whether family functioning is directly related to the academic outcomes of youth with SCD, and investigated whether family functioning moderates the relationships between disease severity, SES, age, and academic outcomes, using simultaneous multiple regression models. The current study utilized data collected at the beginning of phase three of the Cooperative Study of Sickle Cell Disease (CSSCD), consisting of 198 youth aged 6 to 16 years. Family functioning was evaluated using the Family Environment Scale, academic achievement by broad reading and math scores from the Woodcock-Johnson Revised Tests of Academic Achievement, and school competence by the School Competence Scale of the CBCL. Results indicate that family functioning variables were neither directly related to academic outcomes, nor did they moderate the relationship between academic outcomes and other factors. Results also indicated that IQ as measured by the FSIQ of the WISC-III was the most powerful predictor of academic functioning. Limitations and clinical implications are discussed.