Screening a virulent Vibrio strain to study the interactions between bacterial infection and host immune defence is important to resolve large-scale summer oyster mortalities. Using adductor muscle injection we tested the oyster responses to phosphate-buffered saline (PBS), lipopolysaccharide (LPS), or Vibrio strains. Mortalities and stress gene expressions were used to characterize oyster immune responses. At 5 days post injection, the cumulative mortality rates in PBS, LPS, Vibrio tubiashii, Vibrio anguillarum, Vibrio alginolyticus and Vibrio aestuarianus groups were 8%, 16%, 36%, 40%, 40% and 76%, respectively, indicating that V. aestuarianus induced the highest death rate. Two-factor analyses of variance revealed that expression of SOD, CAT, GPX and HSP70 was influenced by bacterial injections in a time-dependent manner. The expression of all genes increased and reached their peak 3 or 12 h after bacterial injection and then decreased. These genes could be applied as immune responsive biomarkers to monitor early changes in oysters in response to bacterial infection. The greatest changes were observed in the V. aestuarianus-injected group, which may indicate that V. aestuarianus could be used as one of the more virulent strains for experimental infections.