Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent colorectal cancer. Although hyperammonemia is known as one of the adverse side effects of 5-FU, a disturbance of consciousness caused by hyperammonemia is not a usual finding. We encountered a case of 5-FU-related consciousness disturbance with respiratory depression. A woman in her sixties was diagnosed with metastatic cecum cancer, involving peritoneal dissemination and hydronephrosis due to retroperitoneal invasion. After resection of the primary lesion, systemic chemotherapy, including capecitabine, irinotecan, bevacizumab and cetuximab, was administered for the metastatic lesions. As a third-line of treatment, the mFOLFOX6 plus bevacizumab regimen was administered. On the second day of the first course, the patient complained of nausea and vomiting. On third day, her consciousness level was deteriorating. The level of ammonia in the blood was abnormally high. Therefore, we diagnosed consciousness disturbance caused by hyperammonemia resulting from high-dose 5-FU infusion. The symptom improved immediately after mechanical ventilation and intravenous infusion. Renal dysfunction is considered a risk factor for hyperammonemia caused by 5-FU, and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU.