Ceftriaxone is commonly used to treat bacterial infections. Encephalopathy is a rare adverse effect of ceftriaxone therapy, and most cases have been diagnosed based on medical history. We report a case of a 73-year-old woman with ceftriaxone-associated encephalopathy, which was confirmed by measuring the ceftriaxone levels in the blood and cerebrospinal fluid. She regularly underwent hemodialysis. She received intravenous ceftriaxone at a dose of 1 g/day for 4 days for enteritis, and mental status began to be disturbed during the therapy. Six days after ceftriaxone discontinuation, her consciousness level rapidly improved. Thus, ceftriaxone-associated encephalopathy was suspected. High ceftriaxone levels in the blood and cerebrospinal fluid were observed while the patient had disturbed consciousness. This case indicated that high ceftriaxone levels in the blood and cerebrospinal fluid were related to development of encephalopathy. The estimation of ceftriaxone levels may be useful for an accurate diagnosis.