ABSTRACT: Ocean acidification affects the fitness of species in coastal and estuarine systems, although interactions among species may alleviate or elevate the responses. Acidification effects on predator-prey interactions were evaluated between the blue crab Callinectes sapidus and eastern oyster Crassostrea virginica. Animals were exposed to 5 pH treatments: (1) control (pH ~8.00), constant pH at (2) 7.10 and (3) 6.75, and cycling pH from (4) 7.10 and (5) 6.75 to ~8.00, respectively. Crab foraging behavior, oyster size, and their defensive response against crabs (i.e. shell thickening) were compared among pH treatments. Results showed that predation rates of crabs tended to decrease with pH and from cycling to constant conditions, though statistical differences were only found at the lowest pH value and when consuming the larger oysters offered. Also, crab interest in oysters decreased with decreasing pH. In contrast, prey handling times and foraging motivation triggered by an odor stimulus were not affected by pH. In oysters, size metrics decreased with pH and also from cycling to constant conditions. Additionally, shells were thicker in the presence of predators, although the defensive strategy of oysters was weakened at the lowest pH level examined. Results indicate that although impaired foraging behavior of blue crabs may compensate for the negative effects on oysters under extreme acidification conditions, net effects are difficult to predict depending on the conditions to which animals are exposed and the size and behavioral variables considered.