Introduction: Academic achievement is crucial for advancing learning goals. For disease-related and possibly additional reasons, children with sickle cell anaemia (SCA) in Sub-Saharan Africa (SSA) may be at risk of disease-associated school difficulties. Limited data exist on academic achievement of school-age children with SCA in the region. We aimed to assess academic achievement of children with SCA in Uganda. Methods: This cross-sectional study was conducted in Kampala, Uganda. Participants were school-going children with SCA, aged 6-12 years, attending Mulago Hospital SCA Clinic, and age-matched sibling controls without SCA. Academic achievement was assessed using the Wide Range Achievement Test, Fourth Edition (WRAT4) using outcome measures of spelling, mathematical computation, word reading, and sentence comprehension by age-normalized Z-scores. Results: Among 68 SCA and 69 controls tested, mean age was 9.4 (SD2.0) years; with males 55.9% and 46.4%, respectively. Mean haemoglobin was 7.9 (0.)g/dL in the SCA group versus 12.8 (0.)g/dL in the controls, (p<0.001). Children with SCA scored lower in spelling, (mean difference [95% confidence interval] -0.36 [-0.02 to -0.69], p=0.04) and mathematical computation, (mean difference [95% confidence interval] -0.51 [-0.17 to -0.85], p=0.003) than the controls. No differences by group were found in word reading or sentence comprehension. In the SCA group, lower scores in spelling correlated with age, and males performed better than females in mathematical computation. Discussion: School-aged children with SCA were at risk of poor performance in spelling and mathematical computation. Our findings suggest their need for educational evaluation and support, especially in these two areas, in SSA.