Hypophosphatemia leads to muscle weakness with preference for the diaphragm but acute hypophosphatemia-induced metabolic encephalopathy is very rare. Here, we report the case of a 43-year-old woman with acute metabolic encephalopathy with severe hypophosphatemia during continuous renal replacement therapy. She presented with features of oliguric acute kidney injury on diabetic kidney disease due to volume depletion. She was alert at admission but gradually mental change during continuous renal replacement therapy. Her brain CT scan revealed normal findings. Her phosphate level was less than 0.41 mEq/L andGlasgow coma scale decreased from 15 to 6. After phosphate intravenous replacement and phosphate containing replacement solution use, her phosphate level increased to 2.97 mEq/L and mental state returned to alert. This case demonstrates that we should observe the level of phosphorus during continuous renal replacement therapy.