A three-year-old Thoroughbred filly presented to Cornell University’s Equine Hospital for colitis and chronic unilateral nasal discharge. The filly had a one month long history of multiple antibiotic treatments to attempt to resolve the chronic nasal discharge. On presentation the filly was quiet, alert, and responsive. Her temperature was within normal limits at 101.4°F, but she was tachycardic with a heart rate of 60 beats/minute and tachypneic with a respiratory rate of 28 breaths/minute. Mucous membranes were bright pink, injected, tacky, and had a toxic line present. Her capillary refill time was prolonged at four seconds. No borborygmi were present, but there was a ‘ping’ present on her upper, right abdomen. Her digital pulses palpated within normal limits and her feet were cold to the touch. Her left nostril had a small amount of mucopurulent discharge present. No feces were present on rectal examination, although her medial cecal band was painful upon palpation and her cecum was distended with gas. Initial blood work supported the physical examination findings of severe dehydration and endotoxemia. Complete blood count and a serum chemistry panel revealed a severe leukopenia, neutropenia with a degenerative left shift and marked toxic changes, thrombocytopenia, and electrolyte derangements consistent with losses through the gastrointestinal tract. Abdominal ultrasound revealed a fluid-filled cecum and large colon, consistent with typhlocolitis. A fecal sample was positive for Clostridium difficile toxins A and B. This report will explore the risk factors, differentials, and initial work-up for Clostridium difficile colitis in a horse. The management, including the use of fecal transfaunation, and complications including laminitis, pulmonary aspergillosis and thrombosis, will also be discussed.