To assess the ability of adult blue crab (Callinectes sapidus) to function under the hypoxic conditions becoming increasingly common in their inshore habitats, critical oxygen levels (i.e., the minimum oxygen levels at which aerobic metabolism can be maintained) were determined over a range of metabolic rates using automated intermittent-flow respirometry. Different metabolic rates were induced by conducting experiments at three temperatures (17°, 23°, and 28 °C), testing recently fed crabs, and those infected with the parasitic dinoflagellate Hematodinium perezi. The effects of hypoxia on the metabolic rates and recovery times of individuals following enforced exhaustive activity, and metabolic rates following feeding, were also measured to determine the levels of hypoxia likely to impact feeding, digestion, and overall energetics. Contrary to previously published results, blue crab were found not to be partial oxygen conformers (i.e., where metabolic rate falls in concert with reductions in ambient oxygen), but rather to be oxygen regulators (i.e., to have the ability to maintain a constant aerobic metabolic rate until the critical oxygen level was reached). By this measure, at routine metabolic rates blue crab are as hypoxia-tolerant as other decapod crustaceans with a median critical oxygen level of ~ 20% air saturation (at 17° and 23 °C). Critical oxygen levels increased in concert with the increases in metabolic rate occurring at 28 °C, in individuals infected with H. perezii, and those recently fed. At the highest metabolic rates (measured in recently fed individuals at 28 °C) median critical oxygen level was ~ 45% air saturation. Consistent with this latter observation, metabolic rates after feeding or exercise were not compromised until below 50% air saturation, although maximum metabolic rates were lower at this level of hypoxia. The results presented are consistent with the oxygen levels shown to influence blue crab behaviors (~ 2 to 4 mg l− 1) in both field and laboratory settings.