The paper discusses the physiological processes limiting thermal tolerance in ectothermic animals, focusing on the role of oxygen limitation. It highlights that metazoans have lower heat tolerance compared to unicellular eukaryotes and bacteria, suggesting a complex systemic process at play. The aerobic scope of whole animals is the first process to be limited at both low and high temperatures, affecting circulation and ventilation. Oxygen levels in body fluids can decrease, reflecting excessive oxygen demand at high temperatures or insufficient aerobic capacity at low temperatures. Aerobic scope declines beyond the thermal optimum and vanishes at critical temperatures when anaerobic mitochondrial metabolism transitions occur. Adjustments in mitochondrial densities are crucial for maintaining aerobic scope and shifting thermal tolerance. The capacity to deliver oxygen matches full aerobic scope only within the thermal optimum, and at extreme temperatures, survival is time-limited, supported by residual aerobic scope, anaerobic metabolism, and molecular protection. The progressive increase in oxygen limitation at extreme temperatures may enhance oxidative and denaturation stress. The paper concludes that the oxygen delivery system, a complex organizational level, defines thermal tolerance limits before molecular functions are disturbed.The paper discusses the physiological processes limiting thermal tolerance in ectothermic animals, focusing on the role of oxygen limitation. It highlights that metazoans have lower heat tolerance compared to unicellular eukaryotes and bacteria, suggesting a complex systemic process at play. The aerobic scope of whole animals is the first process to be limited at both low and high temperatures, affecting circulation and ventilation. Oxygen levels in body fluids can decrease, reflecting excessive oxygen demand at high temperatures or insufficient aerobic capacity at low temperatures. Aerobic scope declines beyond the thermal optimum and vanishes at critical temperatures when anaerobic mitochondrial metabolism transitions occur. Adjustments in mitochondrial densities are crucial for maintaining aerobic scope and shifting thermal tolerance. The capacity to deliver oxygen matches full aerobic scope only within the thermal optimum, and at extreme temperatures, survival is time-limited, supported by residual aerobic scope, anaerobic metabolism, and molecular protection. The progressive increase in oxygen limitation at extreme temperatures may enhance oxidative and denaturation stress. The paper concludes that the oxygen delivery system, a complex organizational level, defines thermal tolerance limits before molecular functions are disturbed.