Nocturnal enuresis is common among children and adolescents with sickle cell disease. Subjects and methods: This is a cross-sectional study that included 78 steady state sickle cell diseased patients attending at Pediatric Hematology Clinic, New Children Hospital, Cairo University. All patients were subjected to full history taking, clinical and laboratory examinations. Results: The prevalence of nocturnal enuresis was 39.7%. The genetic predisposition for nocturnal enuresis was suggested by the significant prevalence of nocturnal enuresis among consanguineous families. Enuretic patients showed higher frequency of polyuria. No association was found between nocturnal enuresis and vasoocclusive crisis or other disease-related morbidity. Conclusion: Further studies are needed to elucidate carefully the underlying pathogenesis of nocturnal enuresis in SCD and to evaluate the role of SCA-related factors in its development. Lack of association of nocturnal enuresis with clinical and laboratory variables in our cohort might indicate that additional psychosocial factors may contribute to the development of nocturnal enuresis.