Previous analyses of New York City (NYC) health department's lead registry indicated that, among children with lead poisoning, an increased prevalence of sickle cell disease (SCD) exists. However, SCD is not considered a risk factor for lead poisoning. We assessed the association between SCD and childhood lead poisoning to determine if specific lead poisoning prevention efforts are needed for children with SCD. We analyzed NYC's lead registry data for children with venous blood lead levels (BLLs) ≥15 mcg/dL during 2005 to 2019. t tests and χ2 tests were performed to compare demographic characteristics, BLLs, and lead exposure risks in non-Hispanic Black children with and without SCD. A t test was used to compare observed SCD prevalence among Black children with BLLs ≥15 mcg/dL with an estimated 0.43% SCD prevalence among Black NYC children. Among 1728 Black children with BLLs ≥15 mcg/dL identified, 37 (2.14%) had SCD. When comparing children with and without SCD, both mean age at peak BLL (62.8 versus 42.7 months; P = .003) and peak BLL (42.59 versus 23.06 mcg/dL; P = .008) were higher for children with SCD. Among risk factors for lead exposure, children with SCD had higher prevalence of pica. Observed SCD prevalence was 1.71% higher than estimated SCD prevalence among Black NYC children (P < .001). We found a potential association between SCD and childhood lead poisoning. Pica emerged as a potentially important risk factor. Our findings might have implications for lead poisoning prevention guidelines for children with SCD.