This study investigated the effects on the physiology of Pacific oyster, Crassostrea gigas, of a mixture of pesticides containing 0.8 μg L−1 alachlor, 0.6 μg L−1 metolachlor, 0.7 μg L−1 atrazine, 0.6 μg L−1 terbuthylazine, 0.5 μg L−1 diuron, 0.6 μg L−1 fosetyl aluminum, 0.05 μg L−1 carbaryl, and 0.7 μg L−1 glyphosate for a total concentration of 4.55 μg L−1. The total nominal concentration of pesticides mixture corresponds to the pesticide concentrations in the shellfish culture area of the Marennes-Oleron basin. Two varieties of C. gigas were selected on the foreshore, based on their characteristics in terms of resistance to summer mortality, to assess the effects of the pesticide mixture after 7 days of exposure under controlled conditions. The early effects of the mixture were assessed using enzyme biomarkers of nitrogen metabolism (GS, glutamine synthetase), detoxification metabolism (GST, glutathione S-transferase), and oxidative stress (CAT, catalase). Sublethal effects on hemocyte parameters (phagocytosis and esterase activity) and DNA damages (DNA adducts) were also measured. Changes in metabolic activities were characterized by increases in GS, GST, and CAT levels on the first day of exposure for the “resistant” oysters and after 3–7 days of exposure for the “susceptible” oysters. The formation of DNA adducts was detected after 7 days of exposure. The percentage of hemocyte esterase-positive cells was reduced in the resistant oysters, as was the hemocyte phagocytic capacity in both oyster varieties after 7 days of exposure to the pesticide mixture. This study highlights the need to consider the low doses and the mixture of pesticides to evaluate the effects of these molecules on organisms. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 689–699, 2013.