Both overfeeding and underfeeding critically ill children are problematic. This prospective pilot study evaluated the resting energy expenditure in infants and children requiring extracorporeal membrane oxygenation (ECMO) support. An indirect calorimeter was used to measure oxygen consumption (VO2) and carbon dioxide production (VCO2) from the mechanical ventilator. Blood gases were used to determine VO2 and VCO2 from the ECMO circuit. Values from the mechanical ventilator and ECMO circuit were added, and the resting energy expenditure (REE) (Kcal/kg/day) was calculated. Measurements were obtained > 24 hours after ECMO support was initiated (day 2 of ECMO), 1 day before ECMO discontinuation or transfer, and 1 day after decannulation. Data were compared with the predicted energy expenditure. Seven patients aged 3 months to 13 years were included. The REE varied greatly both above and below predicted values, from 26 to 154 KCal/kg/day on day 2 of ECMO support. In patients with septic shock, the REE was > 300% above the predicted value on day 2 of ECMO. Before ECMO discontinuation, two of six (33%) children continued to have a REE > 110% of predicted. Three patients had measurements after decannulation, all with a REE < 90% of predicted. REE measurements can be obtained by indirect calorimetry in children receiving ECMO support. ECMO may not provide metabolic rest for all children as a wide variation in REE was observed. For optimal care, individual testing should be considered to match calories provided with the metabolic demand.