High-resolution (downscaled) projections of future climate conditions are critical inputs to a wide variety of ecological and socioeconomic models and are created using numerous different approaches. Here, we conduct a sensitivity analysis of spatial predictions from climate envelope models for threatened and endangered vertebrates in the southeastern United States to determine whether two different downscaling approaches (with and without the use of a regional climate model) affect climate envelope model predictions when all other sources of variation are held constant. We found that prediction maps differed spatially between downscaling approaches and that the variation attributable to downscaling technique was comparable to variation between maps generated using different general circulation models (GCMs). Precipitation variables tended to show greater discrepancies between downscaling techniques than temperature variables, and for one GCM, there was evidence that more poorly resolved precipitation variables contributed relatively more to model uncertainty than more well-resolved variables. Our work suggests that ecological modelers requiring high-resolution climate projections should carefully consider the type of downscaling applied to the climate projections prior to their use in predictive ecological modeling. The uncertainty associated with alternative downscaling methods may rival that of other, more widely appreciated sources of variation, such as the general circulation model or emissions scenario with which future climate projections are created.