Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Although impaired tissue oxygenation is usually responsible for the rise in lactate production, lactic acidosis could be caused by drugs including metformin and the nucleoside reverse-transcriptase inhibitors. Linezolid, an oxazolidinone antibiotic, is currently indicated to treat serious infections caused by van-comycin-resistant enterococcus and other gram-positive organisms. A 74-year old woman was found to have pyogenic vertebral osteomyelitis and treated with linezolid. Thirty-one days after linezolid therapy, she developed severe lactic acidosis. We report a case of lactic acidosis associated with prolonged linezolid therapy.