We report a case of a 40-year-old woman who developed profound polyuria (>25 L urine output) immediately after initiation of venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Investigations into the cause determined the polyuria was due to marked natriuresis (>85 g of sodium excreted in 1 day). This natriuresis persisted despite low cardiac filling pressures and high-negative ECMO venous pressures, suggesting clinical hypovolemia due to pressure natriuresis from locally high pressures at the renal artery due to arterial ECMO inflow. As ECMO flows were decreased, polyuria and natriuresis resolved. To our knowledge, this is the first description of VA-ECMO–associated salt wasting.