Tropical drylands are characterized by extreme environmental conditions that, coupled with anthropogenic habitat degradation, can limit the occurrence of native species. Species that are most sensitive to these pressures may be prone to disappear in the context of climate change. In this study, we evaluated the influence of environmental and anthropogenic variables on the occurrence of large mammals and birds at the Tatacoa Desert, an arid region in central Colombia. We tested the relationship between the magnitude of the species’ responses to environmental, human-related variables and to body mass, and percentage of carnivory. Overall, we found a positive association between forest cover and the occupancy of the largest mammals (> 8kg), negative associations between solar radiation and human footprint with individual species occupancy, and a positive association of species occupancy with distance to touristic sites. Our results suggest that the largest and/or more carnivore species may be affected positively by forest cover and negatively by intense solar radiation highlighting the consequences of the increasing process of desertification on large mammals and birds at the upper Magdalena River basin of Colombia under the current scenario of global climate change.