Cefepime is an extended-spectrum, fourth-generation cephalosporin that has been widely used for approved indications such as febrile neutropenia. Common adverse events of cefepime include headache, skin rash, gastrointestinal problems, and fever. However, encephalopathathy caused by cefepime has been sporadically reported worldwide over the last decade. We experienced a rare case of cefepime-induced encephalopathy. A 75-year-old man with a 30-year history of chronic obstructive pulmonary disease was admitted to the medical intensive care unit under a diagnosis of pneumonia. Initial antibiotic therapy was started with piperacillin/sulbactam and ciprofloxacin. His condition was improved with this treatment. About 2 months later, his condition was aggravated again, with mild fever and purulent sputum. Intravenous cefepime was selected on the basis of antibiotic susceptibility to Pseudomonas aeruginosa isolated from his sputum. However, his mentality became drowsy 48 hours after cefepime adminstration. He showed tremors and right facial paralysis. Neurologic examination for motor power and sensory function revealed normal findings. Laboratory tests, including serum electrolytes, glucose, osmolality, and ammonia, gave normal results. Brain magnetic resonance imaging showed chronic ischemic and atropic changes, and an electroencephalography revealed triphasic waves. The administration of cefepime was stopped, and his symptoms started to improve within 48 hours. Electroencephalography results became normalized, and he completely recovered within 48 hours after discontinuation of cefepime.