The cause of the death of a 16-month-old Brasileiro-de-Hipismo filly and a 3-year-old male Paint Horse with clinical manifestations of anemia and apathy from southern Brazil was investigated. These horses were maintained at the same stable; received hay as part of their diet and were submitted for routine necropsy evaluations. Significant gross findings included several nodules randomly distributed throughout the pulmonary lobes of both horses, and the kidneys, myocardium, and the frontal lobes of the cerebrum of the filly. Histopathological evaluation revealed pyogranulomatous bronchopneumonia in both horses; granulomatous interstitial nephritis, myocarditis, and encephalitis were observed in the filly. All lesions contained vasculitis and thrombosis associated with myriads of intralesional, branching, septate fungi consistent with Aspergillus spp.; intralesional fungi were more easily identified by the Grocott methenamine silver stain. Mycological culture of fresh pulmonary sections from both horses and the brain of the filly revealed pure growths of A. fumigatus. These findings confirmed the participation of A. fumigatus in the etiopathogenesis of the lesions observed in the lungs of both horses, and the cerebrum, myocardium and kidneys of the filly and might represent the first description of A. fumigatus-induced encephalitis in horses. Additionally, we believe that infection occurred during the ingestion of contaminated hay or by inhalation of spores within contaminated bedding that resulted in transient nasal mycosis, which progressed to pyogranulomatous bronchopneumonia in both horses with embolic encephalitic, myocardial, and renal dissemination of A. fumigatus occurring only in the filly.