It is assumed that substrate utilization changes markedly around birth, from mainly glucose utilization before, to glucose/fat utilization after birth. We studied substrate oxidation and turnover in preterm infants on the first day and during the first weeks of life. We found that only part of the glucose that is infused on the first day of life is oxidized, while glucose is also converted into fat at the same time. Almost half of the energy expenditure is provided by fat oxidation on day 7 and 28 of life. Fat oxidation is dependent on the type of fat oxidized; the rate of oxidation of medium chain triglycerides (MCT) is higher than that of long chain fatty acids. MCT can replace glucose as an energy source. Proteins contribute only to a small extent (approximately 7%) to the energy expenditure at all ages.