Vitamin D deficiency has been linked to fracture risk and chronic musculoskeletal pain. Adults with sickle cell disease have a high prevalence of low bone density and chronic pain with poorly defined etiologies. We recognized that vitamin D deficiency may represent a treatable etiology and sought to determine the prevalence of vitamin D deficiency in adults with sickle cell. We measured 25-hydroxy vitamin D levels in adults at 2 university-based sickle cell disease-management programs. Regression was performed in 142 patients to identify predictors of low vitamin D. Mean vitamin D levels were 9.0 ng/mL at Eastern Virginia Medical School and 12.8 ng/mL at University of Chicago; 139 of 142 (98%) had suboptimal levels (<30 ng/mL) and 85/142 (60%) were severely deficient (<10 ng/mL). Vitamin D level was not related to age, sex, hydroxyurea use, sickle cell type, or date of lab draw. Vitamin D deficiency was, therefore, nearly ubiquitous in our patient population, with a majority being severely deficient. Further studies are warranted to evaluate the effects of vitamin D repletion on clinical outcomes such as bone density, chronic musculoskeletal pain, and functional status. Clinicians caring for patients with sickle cell disease should be aware of and screen for this important clinical state.