Background: Children with sickle cell disease have frequent bouts of pain and infection which may increase energy expenditure, decrease energy intake and lead to a subsequent energy deficit. Methods: Two groups of African-American children with sickle cell disease-SS genotype were enrolled in this study upon hospital admission for a sickle cell disease related illness: a younger (<6 years, n = 14, 7 M) and older group (≥ 6 years, n = 17, 8 M). Body composition and dietary intake were assessed, and sleeping (younger) or resting energy expenditure (older) were measured by indirect calorimetry at admission and one month later at steady state. Results: Energy expenditure was not different between the two timepoints for younger children, but was slightly elevated at steady state (+50 kcal/d, P = 0.049) in the older group. After controlling for gender, changes in fat-free mass and dietary intake, the significance disappeared. Energy intake in both groups was significantly depressed at admission compared to follow-up (P < 0.01). Conclusions: These children and adolescents did not expend excess energy during their acute illness, however, an energy deficit was observed secondary to poor energy intake. Since 20% of patients with sickle cell disease have multiple hospitalizations per year, these results provide justification for the development and evaluation of nutrition care protocols to maintain adequate caloric intake during hospitalization and recovery. © 2001 Harcourt Publishers Ltd.