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We explored, using computer simulations, the sensitivity of four mammal species (elk, Cervus canadensis; white-tailed deer, Odocoileus virginianus; Columbian ground squirrel, Spermophilus columbianus; and chipmunk, Tamias striatus) within the continental USA to the effect of anticipated levels of global climate change brought about by a doubling of atmospheric CO2. Sensitivity to the direct effects of climate change were evaluated using a climate-space approach to delineate the range of thermal conditions tolerable by each species. Sensitivity to indirect effects were evaluated by quantifying the association of each species to the current vegetation distribution within the continental USA and using this association to assess whether wildlife species distributions might shift in response to vegetation shifts under climate change. Results indicate that altered thermal conditions alone should have little or no effect on the wildlife species’ distributions as physiological tolerance to heat load would allow them to survive. Analyses of the effects of vegetation change indicate that deer and chipmunks should retain their current distributions and possibly expand westward in the USA. For Elk and ground squirrels, there is a possibility that their current distributions would shrink and there is little possibility that each species would spread to new regions. This work emphasizes that the distributions of the four mammalian species are likely to be influenced more by vegetation changes than by thermal conditions. Future efforts to understand the effects of global change on wildlife species should focus on animal–habitat and climate–vegetation linkages.