Sickle cell disease (SCD) affects approximately 100,000 predominantly African-American individuals in the United States, causing significant cellular damage, increased disease complications, and premature death. The contribution of epigenetic factors to SCD pathophysiology is relatively unexplored. DNA methylation (DNAm), a primary epigenetic mechanism for regulating gene expression in response to the environment, is an important driver of normal cellular aging. Several DNAm epigenetic clocks have been developed to serve as a proxy for cellular aging. We calculated the epigenetic ages of 89 adults with SCD (mean age: 30.64 years; 60.64% female) using five published epigenetic clocks: Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE. We hypothesized that in a chronic disease like SCD, individuals would demonstrate epigenetic age acceleration, but results differed depending on the clock used. Recently developed clocks more consistently demonstrated acceleration (GrimAge, DunedinPACE). Additional demographic and clinical phenotypes were analyzed to determine their associations with epigenetic age estimates. Chronological age was significantly correlated with epigenetic age in all clocks (Horvath, r = 0.88; Hannum, r = 0.89; PhenoAge, r = 0.85; GrimAge, r = 0.88; DunedinPACE, r=0.34). SCD genotype was associated with two clocks (PhenoAge, p = 0.02; DunedinPACE, p < 0.001). Genetic ancestry, biological sex, beta-globin haplotypes, BCL11A rs11886868 and SCD disease severity were not associated. These findings, among the first to interrogate epigenetic aging in adults with SCD, demonstrate epigenetic age acceleration with recently developed epigenetic clocks but not older generation clocks. Further development of epigenetic clocks may improve predictive ability and utility in chronic diseases like SCD.