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Abstract During the late Holocene, the anthropization of environments associated with European colonization in the southern hemisphere caused drastic changes in native ecosystems, leading to numerous extinctions—within Mammalia, 75% correspond to small mammals. We explored the hypothesis of the interaction between body size and diet playing a significant role in their extinction vulnerability. Considering that adaptations to low-protein diets lead to larger body sizes, we propose that this would result in lower fitness for small species with low-protein diets and large species with high-protein (HP) diets. We surveyed bibliographic information on 26 southern hemisphere sites generated by the accumulation of owl pellets to assess composition changes of non-flying small mammal (≤1 kg) communities in the last 1,000 yr, compiled diet and body weight data, and assessed their effect on extinction probability using logistic regressions. We modeled extinction probability for species with high- and low-protein diets as a function of 2 body size variables: absolute weight (average adult weight) and relative weight (an estimator dependent on the dietary group and community)—with sites as a random factor. For both models, we were unable to detect a response of extinction probability to body size for HP species and found an inverse correlation for low-protein species. Our results highlight the potential of studies focused on small mammals by suggesting a close relationship between body size, diet type, and extinction probability—where extrinsic factors such as community composition would also be relevant.