A 6 year old llama was evaluated for an acute onset of neurological behavior. Upon presentation, the llama was obtunded, in lateral recumbency, displaying opisthotonus, and intermittently paddling the hindlimbs. Physical examination revealed cranial nerve deficits, areflexia in all four limbs, increased hindlimb muscle tone and grade III/VI apical heart murmur on the left. Clinicopathologic abnormalities included a mildly elevated lactate, moderate azotemia, marked hyperammonemia and marked elevation of γ-glutamyltransferase (GGT). On ultrasound, approximately 60-80% of the liver parenchyma was effaced by variably sized, encapsulated, irregular masses. Treatment with intravenous isotonic fluids, mannitol, flunixin meglumine and thiamine hydrochloride was attempted, but due to lack of response, the llama was euthanized. Massive hepatocellular necrosis and thromboembolic disease were evident on gross necropsy and confirmed by histopathology. A pure culture of E. coli was isolated from the liver and vascular thrombi. Based on the pattern of lesions, the presumptive pathogenesis of disease was coliform ascension into the portal vein or bile duct, seeding the liver, and causing multifocal septic thrombi throughout hepatobiliary circulatory tree.