An adult male black-necked swan (Cygnus melanocoryphus) was evaluated for a routine physical examination and West Nile virus vaccination. Nine days later, the swan was hospitalized for weakness, dehydration, tremors, and leukocytosis. Gradual clinical improvement was seen over a 2-wk course of supportive care. However, the animal became acutely weak and was found dead. Histopathology revealed severe granulomatous pneumonia and air sacculitis with dissemination to the liver, spleen, intestine, and coelom. Mycobacterial infection was confirmed by identification of acid-fast bacilli within tissue sections and by polymerase chain reaction. Concurrent West Nile virus infection was identified in sections of brain by using immunohistochemistry.