The archaeological site of Payre (South-eastern France) has yielded a remarkable Early Middle Palaeolithic sequence with mixed occupations of Neanderthal and large carnivore occupations ranging from MIS 8 to 6. Recent discoveries during the reassessment of collections brought to light at least a dozen cave (Ursus spelaeus) and brown bear (Ursus arctos) remains bearing cut marks, indicating the in situ carcass processing (skinning, evisceration, dismembering, defleshing) of these large carnivores by early Neanderthals. This is just one of an increasing number of such examples throughout Europe, highlighting once again the diversity of food and non-food resources exploited by these hominins. Furthermore, so far, these discoveries are the sole evidence of large carnivore exploitation by Neanderthal in the western part of the middle Rhône basin, where Palaeolithic sites and Pleistocene bone accumulations are abundant. These new discoveries are put into context with the other known occurrences in Europe. •Large carnivores exploitation played a part in the dietary and cultural behavior of early Neanderthal populations.•Several species of Ursids have been exploited.•Early Neanderthals took advantage of a wide range of resources from these animals.•These practices occurred occasionally on a wide time span covering the Middle Palaeolithic.•Large carnivores exploitation is a Europe-wide phenomenon.