Increasing reliance on the use of triploid oysters to support aquaculture production relies on their generally superior growth rate and meat quality over that of diploid oysters. Reports of elevated triploid mortality have generated questions about potential trade-offs between growth and tolerance to environmental stressors. These questions are particularly relevant as climate change, coastal activities, and river management impact water salinity, temperature, nutrients, pH, and oxygen levels within key estuarine oyster growing areas. In particular, the co-occurrence of warm water temperatures and low dissolved oxygen concentration (DO) events are increasingly reported in estuaries, with potentially lethal impacts on sessile, oyster resources. To investigate potential differences in DO tolerance, diploid and triploid market-sized or seed oysters were exposed to continuous normoxia (DO > 5.0 mg L^–1), hypoxia (DO < 2.0 mg L^–1), and anoxia (DO < 0.5 mg L^–1) at 28°C and their mortalities were monitored. The hemolymph of the market-sized oysters was collected to measure cellular and biochemical changes in response to hypoxia and anoxia, whereas their valve movements were also measured. In general, about half of market-sized oysters died within about 1 wk under anoxia (LT₅₀: 5.7–8.9 days) and within about 2 wk under hypoxia (LT₅₀: 11.9–19.4 days) with diploid oysters tending to die faster than triploid oysters. Seed oysters took longer to die than market-sized oysters under both anoxia (LT₅₀: 9.5–12.1 days) and hypoxia (LT₅₀: 21.8–25.0 days) with diploid oysters (LT₅₀: 9.5–11.8 days) dying slightly faster than triploid oysters (LT₅₀: 11.8–12.1 days) under anoxia. Hemolymph pH decreased and plasma calcium and glutathione concentrations increased with decreasing DO, with values under anoxia being different than those under normoxia. Hemocyte density was also lower under anoxia than under either normoxia or hypoxia. Overall, few differences in physiological responses to hypoxia and anoxia were found between diploid and triploid oysters suggesting that ploidy (2N versus 3N) had limited effect on the tolerance and response of eastern oysters to low DO.