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Introduction: Weight loss after extracorporeal membrane oxygenation (ECMO) has not been previously described. We identified unexpected, severe weight loss in ECMO patients. The goal of this analysis was to quantify this phenomenon, and to estimate the extent to which such weight loss was attributable to hypermetabolism. Methods: This retrospective descriptive study was approved by the local institutional review board and included adult patients who started on ECMO between September 2012 and August 2017, who survived and achieved a dry weight. Patients with burns, amputations, or paralysis were excluded. Weight loss was converted to energy deficit, estimated as 3500 kcal/pound of loss. Energy intake from all sources was recorded from admission to the time at which the lowest near-dry weight was achieved. Data were evaluated with percentage, median, and interquartile range (IQR) using JMP® (Version 13.0.0, SAS Institute, Inc. Cary, NC). Results: Seventeen adult patients were included, 3 were admitted with flu, 1 with inhalational injury, 5 after polytrauma, 2 with cancer, 1 with a bacterial pneumonia, 2 with toxic epidermal necrolysis, and 3 for surgery (back, gastric bypass, and mitral valve). Median age was 33 years (IQR: 27-44); median ECMO duration was 12 days (IQR: 5-17). The median body mass index was 30 kg/m2 (IQR: 25-35). Most (94%) patients experienced weight loss. A median weight loss of 6 kg (IQR: 3-12) occurred over the 29 days (IQR: 18-38) from admission to the time that a dry weight was achieved after initiating ECMO, in spite of a median intake of 1615 kcal/day (IQR: 1358-2300 kcal/day). The usual, healthy, non-injured resting energy expenditure (REE) would be a median of 1661 kcal/day (IQR: 1497-1873 kcal/day) per the Mifflin-ST Jeor equation. Using the weight loss and calorie intake data, we estimate that a median of 3833 kcal/day (IQR: 3111-5085) would be required for weight maintenance, which equates to a median of 45 kcal/kg/day (IQR: 38-62). This is an increase of 2 times (IQR: 2-3 times) the REE of healthy subjects. Conclusions: We show for the first time that most patients on ECMO sustain significant weight loss, indicating an estimated increase in REE to twice normal. Further research is required to determine the energy provision level that is associated with positive outcomes.