Although climate change is predicted to have a substantial effect on the energetic requirements of organisms, the longer-term implications are often unclear. Sloths are limited by the rate at which they can acquire energy and are unable to regulate core body temperature (Tb) to the extent seen in most mammals. Therefore, the metabolic impacts of climate change on sloths are expected to be profound. Here we use indirect calorimetry to measure the oxygen consumption (VO2) and Tb of highland and lowland two-fingered sloths (Choloepus hoffmanni) when exposed to a range of different ambient temperatures (Ta) (18 °C –34 °C), and additionally record changes in Tb and posture over several days in response to natural fluctuations in Ta. We use the resultant data to predict the impact of future climate change on the metabolic rate and Tb of the different sloth populations. The metabolic responses of sloths originating from the two sites differed at high Ta’s, with lowland sloths invoking metabolic depression as temperatures rose above their apparent ‘thermally-active zone’ (TAZ), whereas highland sloths showed increased RMR. Based on climate change estimates for the year 2100, we predict that high-altitude sloths are likely to experience a substantial increase in metabolic rate which, due to their intrinsic energy processing limitations and restricted geographical plasticity, may make their survival untenable in a warming climate.