Objective: To evaluate changes in growth, nutritional status, body composition, and energy and nutrient intakes during illness and usual state of health in infants and young children with sickle cell disease. Design: Sixteen children, aged 0.4 to 5.6 years, with SS type sickle cell disease (SCD-SS) were assessed at the time of hospital admission for an acute illness episode and during an 18-hour overnight follow-up visit 2 to 6 weeks after the acute illness episode when in a state of usual health. Main outcome measures included growth in height and weight compared with reference standards, body composition determined by the skinfold thickness technique and total body electrical conductivity, and dietary intake determined by 24-hour recall during hospital admission and at follow-up. Results: Height, weight, and weight-for-height z scores did not differ from national reference data; triceps skinfold thickness and arm fat area z scores were less. Mean ±standard error body fat was 15.6±2.1% at the time of hospital admission, as measured by total body electrical conductivity, and was not significantly different from the follow-up value (16.2±2.2%). Mean energy intake was 44±9% of Recommended Dietary Allowances at the time of admission and differed significantly from the follow-up value of 90±9% (P<.05). Applications: Infants and children with sickle cell disease appear to be at nutritional risk during an acute illness episode, as indicated by body fat measures and inadequate intakes of energy and macronutrients. Energy intake may be suboptimal for several days surrounding an admission for an acute illness in children with sickle cell disease. Physicians and other health practitioners should be alert to inadequate nutrient intakes of their patients during this time period and may consider supplemental energy to avoid a potential net negative energy balance.