Overfeeding occurs when the administration of calories and/or specific substrate exceeds the requirements to maintain metabolic homeostasis. These requirements are substantially altered during periods of injury-induced acute metabolic stress. Excess nutritional delivery during this period can further increase the metabolic demands of acute injury and place an added burden on the lungs and liver. The result is to increase pulmonary and hepatic pathophysiology, as well as to increase the risk of mortality. It is important, therefore, to ensure that caloric intake not exceed demand. Precise caloric delivery is best determined during acute injury states by measuring energy expenditure. Due to substantial interpatient variability, estimates of energy needs on the basis of disease categories, subject age, or body composition can be misleading and usually result in overfeeding. The delivery of caloric amounts normally required for healthy infants is inappropriate for acutely-stressed, critically ill infants in whom total energy requirements are much lower due to inhibited growth, reduced insensible losses, and decreased activity. Such nutritional administration can result in overfeeding by 200% of measured energy expenditure. Overfeeding cannot reverse tissue catabolism until the acute metabolic stress response has resolved. In these acutely-stressed infants, measured energy expenditure constitutes the total energy requirement, and caloric delivery in excess of this amount should be avoided until metabolic stress parameters indicate resolution of the acute injury state. Enteral delivery should be used in preference to parenteral feeding. Even if total caloric delivery cannot be achieved enterally, the provision of a small amount of the total energy budget via the enteral route is generally possible and is likely advantageous.(ABSTRACT TRUNCATED AT 250 WORDS)