Vitamin D insufficiency affects 33%-78% of children and 60-100% of adults with sickle cell disease (SCD). There are no previous reports demonstrating a correlation between vitamin D insufficiency and cell turnover in patients with SCD. We hypothesized that vitamin D insufficiency was prevalent in our SCD population (ages 0-60 years) and would correlate with reticulocyte counts in these patients. We performed a retrospective cross-sectional review of the medical records of 194 patients (ages up to 60 years) with SCD to evaluate their 25-hydroxyvitamin D levels as a function of red blood cell turnover, patient’s age, number of pain crises, SCD genotype, and Hydroxyurea therapy. Vitamin D insufficiency was present in 88% of children and 96% of adults in our patient cohort. Serum 25-OH vitamin D levels correlated significantly with both age and reticulocyte counts in multiple regression analysis. Furthermore, pediatric HbSS patients had significantly lower 25-OH vitamin D levels than HbSC patients. No significant correlation was found between vitamin D levels and number of pain crises. Based on these findings, vitamin D insufficiency is a function of overall disease severity as manifested by the correlation with reticulocytosis.