Two young American miniature horses from the same farm were evaluated by a veterinarian due to presence of lethargy, anorexia, and cardiac arrhythmias. Both horses were treated aggressively with IV fluids and other supportive measures. The first horse died approximately 72 hr after the start of clinical signs and the second horse was humanely euthanized due to poor response to treatment. Oleander toxicosis was suspected based on the types of clinical signs present and due to several oleander plants and dried leaves present on the property. Oleander toxicosis was confirmed by the presence of oleandrin in gastrointestinal contents and digoxin in the serum of second horse.