Research on the dynamics of body-size changes in varied water depths can provide important insights into the evolution of palaeoenvironments through time. This paper attempts to investigate how the body sizes of two most commonly found chonetid brachiopod species in the uppermost Permian in South China varied with palaeo-bathymetry. The result shows that there is a broadly negative correlation between the latest Permian brachiopod body size and water depth. There is no simple singular variable that could explain this correlation because bathymetry is correlated, either linearly or nonlinearly, to food availability, redox condition and habitat temperature, as well as substrate conditions. Overall, we found that both oxygen and food availability played a more important role in controlling the differences of body sizes, and specifically several depressed factors (low food availability, anoxia, or abnormal temperature) have compounded and caused small body sizes in deeper waters during the latest Permian. We propose that the brachiopod miniaturization during the Permian-Triassic crisis in South China was collectively driven by anoxia, food restriction and high temperature.