The climate crisis necessitates predicting how organisms respond to changing environments, but this requires understanding the mechanisms underlying thermal tolerance. The Hierarchical Mechanisms of Thermal Limitation (HMTL) hypothesis proposes that respiratory capacity and marginal stability of proteins and membranes interact hierarchically to determine thermal performance and limits. An untested prediction of the HMTL hypothesis is that behavioral anapyrexia (i.e., reduced body temperature in hypoxia) is exacerbated when metabolic demand is high. We tested this prediction by manipulating western fence lizards' (Sceloporus occidentalis) metabolic demand and oxygen environment, then measuring selected body temperatures. Lizards with elevated metabolic demand selected lower body temperatures at higher oxygen concentrations than resting lizards, but this occurred only at oxygen concentrations <12% O 2 , suggesting thermal limits are unaffected by naturally-occurring oxygen variation. Given our results and the ubiquity of behavioral anapyrexia, the HMTL hypothesis may generally explain how oxygen and temperature interactively affect reptile performance.