Background: Sickle cell disease (SCD) is a hereditary disorder affecting red blood cells’ shape and functional capacity. Individuals with SCD report relatively high co-occurrence of neurodevelopmental disorders (NDDs). In addition, these children also have higher rates of enuresis (incontinence) and pica, disorders prevalent in children with developmental delays. Both enuresis and pica can have negative effects on mental health, but their pathophysiology, especially in SCD, remains unclear. Objectives: The objective of this study was to determine the rates of pica and enuresis in a pediatric SCD clinic to compare the co-occurrence of NDDs and enuresis/pica. Methods: To do so, we performed a cross-sectional explanatory retrospective chart review of 275 pediatric SCD patients. Results: Our SCD cohort had a 27% prevalence of enuresis, 9% prevalence of pica, and 24% prevalence of one or more NDDs. We noted significant inter-group overlap between pica/enuresis and other risk SCD severity factors. NDDs were approximately twice as frequent in SCD patients with pica or enuresis compared to those without. While pica was associated with HbSβ⁺, it was not linked to disease severity indicators. Enuresis was associated with hydroxyurea usage (66.7% vs. 42.6%, p = 0.001) and reticulocyte counts, indicative of higher disease severity. Conclusions: Clinically, these results are the first to show co-occurrence between pica, enuresis, and NDDs in SCD. We suggest that the occurrence of pica or enuresis may serve as an indicator for previously unknown NDD risk. Together, these results underscore the need for targeted screenings of pica and enuresis in SCD populations.