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Patients with end-stage liver disease are often hyponatremic due to multiple physiological processes associated with hepatic failure. For severely hyponatremic patients undergoing liver transplantation, intraoperative management of serum sodium concentration ([Na]s) is challenging. [Na]s tends to increase during transplantation by the administration of fluids with higher sodium concentration than the patient’s [Na]s. An overly rapid increase in [Na]s (>1 mEq·L−1·hour−1) is difficult to avoid and increases the risk of serious perioperative complications. We report the successful use of intravenous desmopressin to reverse an overly rapid rise in [Na]s during living donor liver transplantation.