Background: Recent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D deficiency (VDD). Moreover, lower levels of vitamin D can affect thyroid function which in turn affects bone formation. Aim: To determine the prevalence of VDD in patients with homozygous SCD and to evaluate the predictors of VDD in them. Method: Relevant data was retrieved from hospital database. Pearsons correlation and Multiple linear regression analysis was performed on these data to assess VDD in patients with SCD. Results: The vitamin D level was remarkably lowered in SCD patients (mean 19.1±14.7 nmol/L vs. 75.9±33.5 nmol/L) when compared to controls (p<0.05). SCD patients had increased ALP levels (161.3±68.0 vs. 61.7±16.6, p<0.001), reticulocyte count (4.18±2.7 vs. 1.07±0.68, p<0.01) and reduced levels of TSH (1.05±0.91 vs. 1.74±1.0, p<0.05). No difference existed between patients of different age groups or gender. Conclusion: A general VDD prevailed in Kuwaiti population but the risk of VDD in SCD-SS was approximately 4 folds higher than control subjects. ALP concentration inversely correlated with vitamin D levels and was the strong predictor of its deficiency.