Background Nocturnal enuresis is a common symptom in children with sickle cell disease (SCD). Risk factors for development of enuresis are currently unknown. An early manifestation of SCD-associated kidney damage is glomerular hyperfiltration. We test the hypothesis that in a pediatric SCD cohort, individuals with hyperfiltration are more likely to have nocturnal enuresis when compared to children without hyperfiltration. Procedures To assess the relationship between nocturnal enuresis and hyperfiltration, we retrospectively evaluated children with SCD enrolled in the Evaluation of Nocturnal Enuresis and Barriers to Treatment among Pediatric Patients with SCD study (PEESC; NCT01959958) and prospectively identified children who reported nocturnal enuresis and were enrolled in the longitudinal cohort study Sickle Cell Clinical Research and Intervention Program (SCCRIP, NCT02098863). Results Nocturnal enuresis occurred in 46.5% of PEESC participants and was more frequent in participants with HbSS/HbSβ0-thalassemia and in male participants. We did not identify an association between hyperfiltration from three to five years of age with the later development of enuresis. Hyposthenuria was not associated with enuresis. Conclusions Severe SCD genotypes and male sex were associated with nocturnal enuresis after age 5 years. However, we could not identify additional renal or hematologic predictors associated with the diagnosis of nocturnal enuresis. Future studies should incorporate non-renal risk factors into studies that predict development of enuresis.