A 4-month-old female domestic shorthair cat was infected by a virus of the Poxvirus family. The animal developed a severe pneumonia and generalized ulcerating lesions of the skin. Histologically, typical eosinophilic intracytoplasmic inclusion bodies indicative of an Orthopoxvirus (OPV) infection were present. The lung showed grey-white to haemorrhagic nodular lesions with a central zone of complete necrosis of alveolar and bronchial tissue. Electron microscopy from skin and lung nodules revealed typical square-shaped OPV particles. Cultivation of the virus on chorio-allantoic membranes of embryonated chicken eggs resulted in haemorrhagic plaques. Restriction enzyme analysis, PCR and sequencing of the D8L gene identified the OPV isolate as a typical Cowpox virus. It was transmitted by the cat to a human contact person who developed a local nodular dermatitis at the inoculation site in association with signs of general infection and had an increase of OPV-specific neutralizing antibodies in paired serum samples.