Red deer (Cervus elaphus) is a flexible species that survived the significant climatic and environmental change toward warming temperature and forested landscape of the Late-glacial to early Holocene transition (ca. 17–6 ka cal BP). To investigate the conditions of ethological adaptation of red deer at that time, isotopic analysis of carbon, nitrogen, sulfur in collagen (δ13Ccoll, δ15Ncoll, δ34Scoll) and of oxygen in phosphate (δ18Op) were performed on red deer from archaeological sites of the French Jura and the western Alps. Fifty out of eighty two samples benefited from direct AMS radiocarbon dating, which confirmed the few number of red deer record during the cold Younger Dryas oscillation (ca. 12.8–11.6 ka cal BP) in Western Europe. The French Jura red deer showed a significant decrease in their δ13Ccoll values and increase in their δ15Ncoll values in the early Holocene compared to the Late-glacial, which is most likely due to the change in environment from open areas with low pedogenic activity to warm dense forests with increasing soil maturity. In contrast, the stable δ13Ccoll and δ15Ncoll values over time in the western Alps were thought to indicate a change to higher altitude for the red deer habitat in this mountainous region. A decrease of the δ18Op values between the Late-glacial and the early Holocene was observed in the western Alps red deer, in contrast to the expected increase with rising temperature which was indeed confirmed for the French Jura red deer. The multi-isotope results pointed to open areas home range at higher altitude for the Alps red deer in the Holocene compared to the previous period. The similarity of the δ34Scoll patterns with those of the δ15Ncoll suggested the primarily influence of soil activity on the 34S abundances recorded by red deer in a purely terrestrial context. Red deer of the French Jura on one hand and of the western Alps on the other hand showed different adaptive response to the global warming of the early Holocene, with an ethological change in the first case and a change in home range in the second case.