The frequent use of continuous positive airway pressure and positive end-expiratory pressure in newborn infants with pulmonary disease has prevented the use of conventional methods for measuring oxygen uptake (VO2) in intensive-care units. A feed-back replenishment technique for the determination of the oxygen uptake of these newborn infants has been developed. An instrument utilizing this method has been designed and built permitting continuous VO2 monitoring without interfering in the routine ventilatory therapy of the critically ill infant. Theoretical, bench, and animal experiments using room air as an inspired gas indicate instrument accuracies as a percentage of full scale of 2.4, 2.8, and 7.3, respectively. Preliminary trials on infants demonstrate that the instrument functions satisfactorily in the newborn intensive-care unit.