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Cave bears (Ursus spelaeus) are an iconic component of the European late Quaternary Ice Age megafauna. Recent demographic analyses based on cave bear mtDNA sequences and refined radiocarbon dating indicate that cave bear population size and genetic diversity started to decline some 50 kilo years ago (kya). Hence, neither the coldest phase of the last glaciation (started some 24 kya), nor the colonization of Europe by Palaeolithic hunters (started some 45 kya) coincides with the beginning of population decline. Here, we reconstructed cave bear climatic niche evolution through time. Then, we performed spatially explicit population viability analyses to assess cave bear demographics through time in response to climatic changes, human effects on bear survival and their combination. We found that climate change was responsible for a 10-fold decrease in cave bear population size after 40 kya. However, climate change on its own could not explain U.spelaeus extinction at 24 kya. Additional negative effects consistent with human population expansion are required to explain both U.spelaeus' retreat from eastern Europe since 40 kya and its final extinction.