The vertebrate fossil record of Cement Creek Cave, Colorado, spans from ≫ 45,000 yr ago to the present and represents the richest stratified series of high-elevation (≫ 2900 m) mammal remains known from the late Quaternary of North America. Stable carbon and oxygen isotope analyses of tooth enamel were used to assess potential ecological responses of two species found commonly throughout the cave, Yellow-bellied marmots (Marmota flaviventris) and Bushy-tailed woodrats (Neotoma cinerea), to late Quaternary climate and environmental changes of the Southern Rocky Mountains. Results indicate that despite such perturbations, the dietary ecologies of both species were maintained across this period. Neither taxon shifted to consuming C4 taxa or different C3 functional groups; similarly, no significant shifts in surface water use were detected. Variations in enamel δ13C were observed, however, that represent the physiological responses of high-elevation plants to changing levels of late Quaternary atmospheric CO2. While our findings extend both the geographic and elevational record of this plant CO2 response, they simultaneously highlight the ecological stability of high-elevation M. flaviventris and N. cinerea during climate changes of late Quaternary magnitude.