Deoxygenation is increasingly problematic in coastal waters globally, with many costal estuaries subject to zones of hypoxia (< 2 mg/L dissolved oxygen) or anoxia (< 0.5 mg/L dissolved oxygen). The presence of hypoxic and anoxic zones can place a unique physiological burden on marine fauna and flora, potentially leading to mass mortality and resulting in dead zones. Anthropogenic stressors, such as increased nutrient input (primarily Nitrogen and Phosphorus), have led to long-term increases of hypoxia in the Chesapeake Bay over the 20th century. Although environmental management policies for the Bay have mitigated hypoxia trends, hypoxia continues to be prevalent through many parts of the Bay. While motile aquatic organisms can change locations to avoid seasonal or long-term bouts of deoxygenation, organisms with sessile adult life stages cannot move to avoid this ecological stressor. The Eastern Oyster (Crassostrea virginica) is a foundational species in the Chesapeake Bay’s ecosystem, performing many ecosystem services such as water filtration, nutrient cycling, and fostering benthic-pelagic connectivity while also serving as an economic resource for commercial fishing. However, long-term trends in hypoxia and anoxia, combined with other anthropogenic stressors, have contributed to a decline in Eastern Oyster in the Bay, leaving populations at a fraction of historical levels, fostering a need for research to better understand the physiological and biomechanical responses of C. virginica to depletion of dissolved oxygen. While the Eastern Oyster has been termed a champion of hypoxic tolerance, and studies have been published exploring the impacts of low DO on oyster mortality and sublethal responses, research is still in search of answers to whether the response of the oyster comes from shell-based behavioral resilience to isolate the animal from environmental conditions, or physiological adaptions from the tissue of the oyster. By drilling holes of three different sizes into one valve of the oyster and exposing it to anoxic external conditions, this study aims to bridge the gap in knowledge of whether anoxic tolerance is a behavioral or physiological response. Oysters with a hole drilled in the shell of any size experienced much faster mortality in anoxic environments than oysters with no hole in the shell (χ2= 8, p = 0.005), while the size of the hole drilled did not impact time to death. These results shed new light on the behavioral response of the Eastern Oyster to depleted dissolved oxygen and the importance of clamping to ostracize internal tissue from environmental deviations.