A 4-yr-old male ferret (Mustela putorius furo) was presented with a 3-day history of pelvic limb ataxia and weakness. A cellulitis associated with a deep bite wound was identified and initially treated with antibiotics and anti-inflammatory medication. Two weeks later, a grade IV/VI cardiac murmur was identified on physical examination. Echocardiographic examination revealed irregular thickening of the aortic valve leaflets, with normal chamber dimensions and normal systolic function. The ferret's physical condition rapidly deteriorated and it was subsequently euthanatized. Myxomatous degeneration of the aortic valve leaflets, with ulceration and vegetative lesions, and multiorgan infarctions were identified during necropsy. A bacterial etiologic agent was not identified from blood culture or histopathology. Lesions present were consistent with nonbacterial thrombotic endocarditis, a novel condition in the ferret.