Extreme warming at the end-Permian induced profound changes in marine biogeochemical cycling and animal habitability, leading to the largest extinction in Earth's history. However, a causal mechanism for the extinction that explains the different proxy evidence has yet to be found. By combining recent modeling developments with global and local redox observations, we show that a temperature-driven increase in microbial respiration can reconcile reconstructions of the spatial distribution of euxinia and seafloor anoxia spanning the Permian/Triassic transition. We illustrate how enhanced metabolic rates would have strengthened upper ocean nutrient recycling, and thus shoaled and intensified the oxygen minimum zones — eventually causing euxinic waters to expand onto continental shelves, poisoning benthic habitats. Finally, we find that the temperature effect on microbial activity can account for some of the decline in carbon isotopes at the end-Permian with the implication that carbon release as inferred from those changes is likely overestimated. Our findings present a novel view of the sensitive interconnections between temperature, microbial metabolism, ocean redox state and carbon cycling during the end-Permian mass extinction with potential far-ranging implications for the interpretation of carbon cycle perturbations during Earth history.