Pooled data from studies that were weighted for sample size show an average increase in whole body oxygen consumption (˙VO2 wb) of 2.0 mL/kg/min in acute and chronic lung disease compared to control LBW infants without significant lung disease. This has been poorly understood. We measured˙VO2 wb by indirect calorimetry and simultaneously determined systemic oxygen uptake (˙VO2 Fick) as the product of cardiac output(echocardiography) and the arterial - mixed venous oxygen content difference(cooximetry) assuming that ˙VO2 wb - ˙VO2 Fick accounts for the oxygen consumption of the lung (˙VO2 lung). Right atrial blood samples were used to determine mixed venous oxygenation, and infants were excluded if those samples returned saturations > 89%. Eleven infants(BW 1,076 ± 364 g; GA 28 ± 3 wks; [horizontal bar over]x± SD) undergoing mechanical ventilation for RDS were studied in their first week of life. ˙VO2 lung was 2.02 ± 1.6 mL/kg/min representing 27% of their whole body oxygen uptake (7.58 ± 1.5 mL/kg/min). ˙VO2 lung did not correlate with clinical measures of acute disease severity. However, infants with most severe radiographic changes on followup X-ray series to 28 days of life (Edwards score 5 as assessed by radiologist blinded for ˙VO2 data) all had a ˙VO2 lung> 2.0 mL/kg/min. We conclude that ˙VO2 lung can account for the elevated metabolic rate in LBW infants with lung injury. We speculate that this reflects in part inflammatory pulmonary processes and may herald chronic lung disease.