Previous research has established subtle neurocognitive delays in children with SCD, but whether these deficits have functional impacts in terms of early school performance is unknown. The current study examined whether children with SCD demonstrated deficits relative to healthy peers in school readiness at the start of kindergarten and school performance over the first two years of school. In addition, the relationship between markers of disease severity in the form of rates of ER visits and hospitalizations and school performance in the SCD group was examined, as was the relationship between school resources and school performance for the SCD group. A teacher-report performance assessment of school readiness skills that was administered to children across the state of South Carolina during their 5K and 1st grade academic years was utilized as the primary outcome measure. Results did not support differences between the SCD group and peers on school performance as measured by the teacherreport measure. Markers of disease severity were found to be correlated with school performance as measured by the teacher-report measure. No relationship was found between variables of school resources and school performance. Descriptive analyses revealed significant ceiling effects for the teacher-report measure that could be attenuating statistical effects. Exploratory analyses revealed that children with SCD had significantly higher rates of grade retention compared to controls (9% versus 6%), suggesting that children with SCD may be experiencing more difficulties with academic attainment at the start of formal schooling that is not being captured by the outcome measure utilized in this study.