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To determine red blood cell (RBC) folate and serum vitamin B12 levels in children with sickle cell disease, SS-type, and to evaluate the associations of these nutrient levels with growth and hematologic parameters.Subjects enrolled in this prospective, cross-sectional study were recruited from one tertiary care setting. Complete blood counts, measurement of red blood cell (RBC) folate and serum vitamin B12, anthropometric measures (height, weight, skinfold measurements), pubertal status, and 24-hour dietary recalls were obtained from 70 patients ages 1 to 19 years.Low RBC folate levels were found in 15% of the children. Fifty-seven percent of the sample had inadequate dietary folate intake. Three percent of the children had low serum vitamin B12 levels. All children and adolescents sampled had adequate dietary intake of vitamin B12. Both RBC folate (P = 0.01) and serum vitamin B12 levels (P0.01) decreased with increasing age.More than half of the subjects had inadequate intake of folate from food, and despite daily folate supplementation, 15% had low RBC folate levels. Low serum vitamin B12 levels were rare, and dietary vitamin B12 intake was adequate. Additional research is needed to explore the effects of improved folate status, the need for folate supplementation, and the relationship of folate, vitamin B12, and homocysteine levels and the risk for vascular damage and stroke in children with sickle cell disease.