Infiltrative bowel disease is an important cause of weight loss and cachexia in horses and likely occurs more commonly than is diagnosed. This case demonstrates the challenges of diagnosis and treatment of horses with infiltrative bowel disease. The clinical signs of weight loss with a ravenous appetite and normal manure were highly suggestive of malabsorptive disease, however it was essential to rule out organ failure and other more common causes of weight loss (dental disease, parasitism, etc.). In this case report, oral glucose absorption testing was performed and revealed delayed absorption. Gastric and duodenal pinch biopsies were obtained through gastroduodenal endoscopy and revealed eosinophilic and lymphocytic-plasmacytic enteritis. The horse was treated with parenteral dexamethasone and modifications in diet. Unfortunately, the horse was euthanized after about 1 month of treatment due to a lack of improvement.