Canine distemper virus (CDV) is a worldwide distributed RNA virus that can cause severe disease in carnivore and non-carnivore species. Red foxes are highly susceptible and may act as a reservoir of the virus. As in other wild species, distemper in red foxes can manifest as acute, systemic and chronic nervous form. In the present study, we detected antibodies against CDV among red foxes in Western Serbia, and analyzed histopathologically and immunohistochemically for CDV nuclear protein antigen (CDV-NP) brain samples derived from seropositive animals. Seroprevalence of CDV antibodies was 36.8%. Histopathological changes included gliosis, neuronal degeneration, satellitosis, mononuclear inflammation, demyelination and presence of inclusion bodies. Immunostaining showed a diffuse presence of CDV-NP antigen, mainly in the cytoplasm of astrocytes and neurons. Results of this work contribute to the opinion that red foxes act as a potential reservoir of CDV and underline the importance of routine vaccination of dogs that could come in close contact with these animals. Potential active surveillance program would give a better insight in the degree of CDV infection in wildlife.