Fish thermal and hypoxia tolerances directly determine the capacity of species to persist during low flow periods when water temperatures are high, and waterbodies can become highly stratified. Chronic thermal stress can compound the impacts of acute hypoxic events on fish resulting in significant fish mortality; however, it is not known if the allometric scaling of physiological processes means some size classes are disproportionately affected. We investigated the physiological responses of Murray cod (Maccullochella peelii) over a four-fold body size range (0.2–3000 g) to acute changes in water temperature and oxygen concentration following 4 weeks of acclimation to representative spring (20°C) and summer (28°C) water temperatures. Acclimation to elevated water temperatures improved thermal and hypoxia tolerance metrics across all size classes. However, body size significantly affected thermal and hypoxia responses. Small M. peelii were significantly less hypoxia tolerant than larger individuals, while larger fish were significantly less thermal tolerant than smaller fish. Hypoxia constrained thermal tolerance in M. peelii, with both small and large fish disproportionally compromised relative to mid-sized fish. This research will inform understanding of the critical flow and temperature requirements of Murray cod for the upcoming Condamine & Balonne water plan review.