Horses that present to referral facilities with colic are often afflicted with severe gastrointestinal disease that may have important secondary complications such as endotoxemia. It is important to recognize the relationship between gastrointestinal disease and the development of endotoxemia in horses, and how these diseases are concurrently expressed clinically. The treatment of horses that present with colic must address the primary gastrointestinal disease as well as consider treatments to address the risks associated with the development of endotoxemia. The high incidence of endotoxemia in these horses may require clinicians to consider endotoxemia as another primary disease when developing their treatment plans.