An 81-year-old woman with extensive peripheral vascular and coronary artery disease was admitted to the intensive care unit with a deep heel abscess and urinary tract infection. When cultures from the heel ulcer yielded vancomycin-resistant enterococci, she was started on the antibiotic linezolid. After several days of intravenous linezolid therapy, she developed severe lactic acidosis (pH 6.89) and elevation of pancreatic enzymes. An emergent exploratory laparotomy was performed to rule out mesenteric ischemia. Findings from the laparotomy were negative, and after elimination of other differential diagnoses, the metabolic acidosis was ultimately attributed to linezolid. Acidosis resolved after discontinuation of linezolid.