Increasing drought frequency and duration pose a significant threat to fish species in dryland river systems. As ectotherms, thermal and hypoxia tolerances directly determine the capacity of fish species to persist in these environments during low flow periods when water temperatures are high and waterbodies become stratified. Managing the ecological function of dryland river refugia requires an understanding of how chronically elevated temperatures and hypoxia affect fish physiological performance, and their capacity to compensate performance in response. We studied the effects of chronic high temperature (30oC) or chronic hypoxia (50% air saturation) on two species of freshwater fish, golden perch Macquaria ambigua, and Murray cod, Maccullochella peelii. In both species, cross tolerance resulted in improved hypoxia and thermal tolerance limits following acclimation to either chronic hypoxia or high temperature. Physiological plasticity of the heart also resulted following acclimation to hypoxic waters in golden perch, increasing in size to support an elevated oxygen transport capacity. In Murray cod, 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 thermally tolerant than smaller fish. Our data suggests that acclimation to elevated temperature or elevated hypoxia can improve both hypoxia and thermal tolerance limits in some fish species, but that responses man differ across size classes. This information will be critical in developing habitat suitability models to inform policy decisions that serve to balance competing demands on freshwater resources in dryland rivers.