Serotonin syndrome (SS) is a potentially life-threatening drug reaction characterized by mental status change, increased neuromuscular tone, and autonomic instability. Linezolid, an oxazolidinone antibacterial agent, is widely used in general hospitals; however, it interacts with some serotonin agonists and may cause SS. We report a case of SS caused by linezolid, without the concomitant use of serotonin agonist. A 72-year-old patient was admitted due to recurrent wound infection of his left ankle. He developed fever, skin rash, and renal function deterioration, and blood eosinophils and liver enzymes increased after administration of vancomycin. The antibiotic was changed to linezolid against methicillin-resistant Staphylococcus aureus. Four days later, he developed agitation, fever, increased blood pressure, and tachycardia. There were no abnormal findings in laboratory and image tests, including brain and chest computed tomography suggesting the cause of his symptoms. He had not taken any serotonin agonists, including serotonin uptake inhibitors and monoamineoxidase-inhibiting antidepressants. When administration of linezolid was stopped, his symptoms improved within 24 hours and fully recovered within 2 days without additional treatments.