Objective: Sickle cell disease (SCD) is associated with neurocognitive and academic impairment. Routine screening is recommended to evaluate for possible concerns. This paper describes results from a neurocognitive screening battery and evaluates relationships with psychosocial and medical variables. Methods: Participants included 61 patients stratified among three age groups, including ages 6-7, ages 11-12, and ages 15-16. Patients completed a screening assessing cognitive performance, academic functioning, and attention (older subjects completed a task of executive function) and a measure assessing HRQL. Caregivers completed a clinical interview and forms evaluating HRQL, executive functioning, and attention. The impact of relevant medical variables and socio-economic status (SES) was also considered. Results: Between 20% and 33% of participants scored ≤ 1 SD below age-based means on intellectual subtests, and between 31 and 48% scored ≤ 1 SD below grade-based means on academic subtests. Attention concerns were noted in 25% of patients, while 20-31% of parents reported executive function concerns. Neither disease subtype nor hemoglobin were associated with cognitive or academic functioning. There was an association between mean corpuscular volume (MCV) and both cognitive abilities and psychosocial health. Cognitive scores were correlated with SES, suggesting an impact of socioeconomic disparities on performance. Conclusions: Sickle Cell Disease negatively impacts cognitive and academic functioning both directly and indirectly due to pain, missed school, and through socioeconomic and racial disparities. These concerns may increase over time as disease processes and medication compliance often worsen. Longitudinal research is needed to further explore these trends.