In this paper, biochemical and physiological analyses were used to characterize changes associated with mortality event occurred during veliger development of American oyster, Crassostrea virginica. Biochemical analyses included the evaluation of lipid classes, fatty acid composition and total protein content. Larval physiology was evaluated by studying feeding activity, enzymes related to energy metabolism, oxidative stress levels and enzymatic antioxidant defenses. These analyses were complemented by bacterial community analyses as well as by measuring larval oyster performance. We observed that mortality events coincided with (1) strong changes in the surrounding bacterial community; (2) a progressive decrease in feeding activity; (3) higher levels of some lipid classes (free fatty acids, diglycerides, and acetone mobile phospholipids); (4) lower levels of phospholipids and protein; (5) higher contents of non-methylene interrupted dienoic fatty acids (22:2 NMI); (6) a decrease in energy metabolism activity (citrate synthase and cytochrome oxidase activities); (7) a higher oxidative stress (lipid peroxidation level); and (8) an activation of antioxidant defences before mortality (glutathione peroxidase and superoxide dismutase). We hypothesized that mortality emergence was related to higher energy consumption coupled with the progressive decline in feeding activity, lowered energy reserves and a decrease in energy metabolism activity. Thus, the low energy availability limited the efficiency of antioxidant defenses, resulting in a higher oxidative stress.