SummaryWe measured blood flow to the myocardium of the left ventricular free wall, and blood glucose, lactate, pyruvate, and oxygen concentrations simultaneously in the aorta and coronary sinus 13 times in seven previously instrumented newborn sheep, 4 to 25 days after birth. We calculated arteriovenous difference and consumption of oxygen, glucose, lactate, and pyruvate by the newborn myocardium. Results were compared with recently obtained measurements in the myocardium of fetal and adult sheep (6).Myocardial consumption of oxygen in the newborn (577 ± 38 &mgr;M·min−1·100 g LV−1) was higher than in either the fetuses or the adults. This was associated with a greater myocardial blood flow (201 ± 21 mm·min−1·100 g LV−1) in the newborns. However, the increased myocardial oxygen consumption in the newborns was commensurate with their increased cardiac work as compared with both the fetuses and adults.Although there is an abrupt postnatal increase in arterial glucose concentration, there was no significant difference in either the myocardial consumption of glucose or the contribution of glucose to the total myocardial energy supply among fetal, newborn or adult sheep. Postnatal decreases in myocardial consumption of lactate and pyruvate are not compensated for by an increase in glucose consumption. In newborn sheep, carbohydrates including glucose, lactate, and pyruvate supply the substrate for no more than approximately one‐fourth of the total myocardial energy demands (carbohydrate/oxygen quotient was 0.26).SpeculationAlthough glucose and lactate supply most of the substrate for myocardial energy supply in the lamb fetus, postnatally there is an abrupt decrease in lactate utilization that is not compensated for by an increase in glucose utilization. The identity of the primary myocardial energy substrate(s) in newborn and adult sheep remains to be determined.