A 4-yr-old tiger (Panthera tigris) was referred with acute onset of severe abnormal consciousness. Neurological evaluation showed normal palpebral and corneal reflexes, normal pupil diameter with normal direct and consensual papillary light reflex, and absent menace response bilaterally. Diffuse forebrain lesion or focal lesion affecting the ascending reticular activating system was suspected. Complete blood examination and cerebrospinal fluid analysis were normal. Magnetic resonance imaging of the brain showed an empty sella as the only result. Clostridium perfringens 10(4) to 10(7) colony-forming units/g were detected in fecal flora samples. Multiplex polymerase chain reaction assay identified serotype B counts with production of epsilon toxin. This toxin specifically accumulates in the central nervous system, where it causes acute neurological signs in humans, domestic animals, and wildlife. In this communication, the acute onset of neurological signs without evidence of trauma, vascular, metabolic, or inflammatory diseases may be caused by neurotoxicity due to C. perfringens.