Stone tool manufacture and use are considered key adaptations in human evolution. The understanding of the biomechanical features and anatomical constraints of hominins during stone tool production have received increased attention in recent years. Similarly, research on the cognitive capabilities and manipulative complexity involved in toolmaking is in progress. However, data on the palaeophysiological constraints of stone knapping are scarce. The balance between energy acquisition and energy expenditure is a key factor to determine the fitness of any individual, and stone knapping is essential for resource procurement in any Palaeolithic society. Thus, the combination of energetic analyses and experimental archaeology provides an excellent tool to improve our understanding of prehistoric behaviours. Here, we present experimental research on the energetics of stone tool production that involves nine experienced subjects. Each subject produced three handaxes through direct hard- and soft-hammer percussion in a total of 27 experiments of toolmaking. All knappers were described by their anthropometric data, and their energetic expenditure was monitored in a breath-by-breath indirect calorimetry procedure. Because knapping is considered a light-intensity level activity, based on its MET (Metabolic Equivalent Task of Intensity) value, our results show some differences in net energy expenditure between direct hard percussion and soft percussion knapping during the configuration of a handaxe. Furthermore, our results suggest that the brachial index of the subjects represents an anatomical constraint for stone knapping because the lever of a shorter forearm reduces energy expenditure during striking and represents an advantage during handaxe production. Differences in the energetic efficiency of knapping, even if they are low, may increase the general fitness of the individual and, indeed, its survival.