The Eastern oyster, Crassostrea virginica, is a sensitive bio-indicator of environmental changes ranging from tidal flux to heavy-metal pollution. Extreme fluctuations in dissolved oxygen levels are well documented in Mobile Bay, AL. Extended periods of low dissolved oxygen occurring during the summer months have been shown to cause oyster mortality. The current study examined the effects of anoxia on tubule morphology of the digestive gland in the Eastern oyster as well as the quantity and quality of whole-body anaerobic bacteria counts. Oysters were exposed to anoxic conditions (<0.1 mg/L O2) at 28°C in a laboratory setting and sampled at 0 h (preexposure), 24 h, 48 h, and 60 h, and after a 4-wk recovery interval. The whole-body anaerobic bacteria count for test oysters (Mean = 1.11 × 106 cfu/mL) from the 60-h interval was significantly higher than counts for the preexposure oysters, 24-h, and 48-h experimental intervals. The most common bacteria isolated were Clostridium sp. Histological examination of oysters exposed to anoxic conditions indicated stress in the digestive gland. Changes in shape and size of digestive tubule epithelial cells occurred, as well as sloughing of secretory absorptive cells into the digestive tubule lumen. Necrosis and inflammation composed of aggregates of hemocytes along with bacterial infiltration into digestive tissue was noted in oysters exposed to anoxic conditions. Digestive tubule lumen ratios of oysters sampled after a 60-h exposure to anoxia were increased significantly in comparison with preexposure oysters. Digestive tubule lumen ratios returned to preexposure morphology after a 4-wk week recovery period. Oysters have the ability to regenerate digestive gland tissue if environmental conditions return to normal. These findings indicate that anoxia exposure at summer temperatures contributes to digestive gland atrophy and necrosis in C. virginica. The combination of digestive gland atrophy, necrosis, and bacterial infiltration into digestive tissues suggests that oysters may be succumbing to infection during periods of anoxic stress.