The characterization of viral respiratory pathogens in snakes is limited in veterinary medicine. Viral respiratory disease in snakes has primarily been noted to be caused by the ophidian paramyxovirus and reovirus. This report describes the clinical and pathological findings of a fatal respiratory disease outbreak in a large snake collection and the identification of a novel nidovirus as the causative agent. The outbreak occurred in a large privately owned snake collection consisting primarily of ball pythons used for breeding. Affected snakes ranged from one to eight years of age on the date that respiratory signs were first observed. The presentation of clinical signs included excessive mucus in the oral cavity, dyspnea, stomatitis, and variable anorexia. Bacterial cultures were submitted on swabs taken from either the oral cavity and/or trachea or from a tracheal wash sample. Of the cases likely to be related and caused by the same causative agent, approximately three-quarters died. Postmortem gross and histological examination was perfonned on several of the snakes with findings primarily restricted to the respiratmy and upper gastrointestinal tracts. Tissue samples were obtained for total nucleic acid extraction and used for viral analysis ultimately leading to the identification of a novel nidovirus.