Growth retardation is common in children with SCA, in spite of adequate dietary intakes. Previous studies have demonstrated elevated REE in children with SCA. An increased metabolic rate may be secondary to rapid hemolysis of sickled cells and the compensatory erythropoietic activity. The purpose of the current investigation was to determine whether the elevated REE in children with SCA can be normalized by RBC transfusion therapy. Five children aged 12 to 16 years (4 males, 1 female) were studied before and one week after a scheduled RBC transfusion. Measurements included anthropometics (height, weight), REE by indirect calorimetry, hemoglobin, reticulocyte count, and percent HgS. Growth failure was seen in 3 of 5 subjects who were below the 25% ile by NCHS standards for height. Pre-transfusion REE was significantly elevated above predicted REE (28%, p≤0.04, Wilcoxon matched-pairs signed-ranks test) consistent with reports in the literature. Surprisingly, REE increased further after RBC transfusion to 37% on average above predicted REE (pre versus post REE, p≤0.08) despite a significant decrease in erythropoietic activity (reticulocyte count: Δ = -9.3%, p≤0.04). Four of 5 subjects showed an increase in REE after RBC transfusion. The subject who had no change in REE demonstrated an increase one week after receiving a second RBC transfusion. Anemia improved after RBC transfusion with an increase in hemoglobin (Δ=1.5 g/dl, p≤0.04), and decrease in Hgb S (Δ=-31.4%, p≤0.04). These results suggest that REE is not correlated with erythropoietic activity in children with SCA and may, in fact, increase when RBC transfusion decreases erythropoietic activity. A possible explanation for this increase includes the hypothesis that a relatively hypoxic catabolic hypermetabolism exists prior to RBC transfusion that transitions in children with SCA to a more hypermetabolic anabolic state after RBC transfusion. If proven, this might explain the catch-up growth observed in children with SCA who receive chronic RBC transfusion therapy.