What the body temperature and thermoregulation processes of extinct vertebrates were are central questions for understanding their ecology and evolution. The thermophysiologic status of the great marine reptiles is still unknown, even though some studies have suggested that thermoregulation may have contributed to their exceptional evolutionary success as apex predators of Mesozoic aquatic ecosystems. We tested the thermal status of ichthyosaurs, plesiosaurs, and mosasaurs by comparing the oxygen isotope compositions of their tooth phosphate to those of coexisting fish. Data distribution reveals that these large marine reptiles were able to maintain a constant and high body temperature in oceanic environments ranging from tropical to cold temperate. Their estimated body temperatures, in the range from 35° ± 2°C to 39° ± 2°C, suggest high metabolic rates required for predation and fast swimming over large distances offshore.