Introduction In winter 2021/2022, a wolf population in the primeval Białowieża Forest in Poland was struck by an outbreak of severe mange caused by mixed infestations of Sarcoptes and Demodex mites. We present an epidemiological analysis of this mange which caused significant morbidity and mortality. Material and Methods Ten sites known for wolf activity were monitored by camera trapping. A diagnostic necropsy and testing of a young wolf was performed to determine the causes of death. Results Five young wolves with severe alopecia of the entire body and some other individuals with minor to medium mange lesions were identified by the camera surveillance. The necropsy of the carcass revealed emaciation, dehydration and anaemia with starvation as the cause of death, likely attributable to severe infestation with Sarcoptes scabiei and Demodex sp. mites. Rabies and infections with Borreliella sp., Anaplasma sp., Ehrlichia sp., Francisella tularensis, Babesia sp. and tick-borne encephalitis virus were excluded by specific tests. Conclusions The described analysis is the first documented co-infestation of this kind in wolves. The outbreak coincided with very mild winter conditions with a high average minimum temperature, which may have favoured mite survival outside the host, and light snowfall, which may have influenced the wolves’ ability to hunt. Other potential drivers of the outbreak could be the large proportion of wetland terrain, increasing number of wolves in the area and anthropogenic pressure on their habitats including the migration crisis at the Polish–Belarusian border and the increased presence of military and border forces, even despite the relief from the anthropogenic pressure from tourism due to the COVID-19 lockdown.