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To evaluate the extent to which sitting position and applied positive end-expiratory pressure improve respiratory mechanics of severely obese patients under mechanical ventilation.Prospective cohort study.A 15-bed ICU of a tertiary hospital.Fifteen consecutive critically ill patients with a body mass index (the weight in kilograms divided by the square of the height in meters) above 35 were compared to 15 controls with body mass index less than 30.Respiratory mechanics was first assessed in the supine position, at zero end-expiratory pressure, and then at positive end-expiratory pressure set at the level of auto-positive endexpiratory pressure. Second, all measures were repeated in the sitting position.Assessment of respiratory mechanics included plateau pressure, auto-positive end-expiratory pressure, and flow-limited volume during manual compression of the abdomen, expressed as percentage of tidal volume to evaluate expiratory flow limitation. In supine position at zero end-expiratory pressure, all critically ill obese patients demonstrated expiratory flow limitation (flow-limited volume, 59.4% [51.3–81.4%] vs 0% [0–0%] in controls; p < 0.0001) and greater auto-positive end-expiratory pressure (10 [5–12.5] vs 0.7 [0.4–1.25] cm H2O in controls; p < 0.0001). Applied positive end-expiratory pressure reverses expiratory flow limitation (flow-limited volume, 0% [0–21%] vs 59.4% [51–81.4%] at zero end-expiratory pressure; p < 0.001) in almost all the obese patients, without increasing plateau pressure (24 [19–25] vs 22 [18–24] cm H2O at zero end-expiratory pressure; p = 0.94). Sitting position not only reverses partially or completely expiratory flow limitation at zero end-expiratory pressure (flow-limited volume, 0% [0–58%] vs 59.4% [51–81.4%] in supine obese patients; p < 0.001) but also results in a significant drop in auto-positive end-expiratory pressure (1.2 [0.6–4] vs 10 [5–12.5] cm H2O in supine obese patients; p < 0.001) and plateau pressure (15.6 [14–17] vs 22 [18–24] cm H2O in supine obese patients; p < 0.001).In critically ill obese patients under mechanical ventilation, sitting position constantly and significantly relieved expiratory flow limitation and auto-positive end-expiratory pressure resulting in a dramatic drop in alveolar pressures. Combining sitting position and applied positive end-expiratory pressure provides the best strategy.