Thirteen aerobic, mesophilic marine bacterial strains were isolated from the pallial (mantle) cavity fluids and associated mucus of the eastern oyster Crassostrea virginica Gmelin. All strains were Gram-negative and identified to genus using 16S RNA gene sequence analysis. Each isolated strain was tested for its ability to inhibit growth of six Gram-negative and five Gram-positive bacterial tester strains, as well as the yeast Candida albicans, using an in vitro agar diffusion screening method to detect antimicrobial activity (Romenenko et al. 2008). All of the marine bacteria isolated from the oyster pallial cavity fluids showed some ability to inhibit tester strains. Two isolates, F (red) and M, inhibited the greatest variety of indicator strains and produced the largest zones of inhibition. Gram-negative indicator strains were more susceptible to antimicrobial activity of pallial fluid isolates than Gram-positive strains. None of the isolated bacteria was shown to inhibit C. albicans. In addition, targeted 16S metagenome libraries from the Chesapeake Bay were screened for the presence of bacteria isolated from this study. Results indicate that there are commonalities between bacteria associated with oysters from Long Island Sound and the Chesapeake Bay systems.