Severe hypernatremia-induced rhabdomyolysis with acute kidney injury is an uncommon and potentially life-threatening clinical event. We reported the case of a 67-year-old woman with acute respiratory distress syndrome. Rhabdomyolysis with acute kidney injury was noted, and the etiology of rhabdomyolysis was hypernatremia. Because of the patient's hypernatremia, fluid overload and unstable hemodynamic status, she was placed under continuous renal replacement therapy. This report highlights an unusual cause of rhabdomyolysis in an acute respiratory distress syndrome patient and the experience of managing such a difficult clinical situation.