Oyster populations are often structured by both biotic interactions and abiotic stresses. Juvenile oysters, i.e., those most vulnerable to predation, face a wide range of predatory characteristics (size, mobility) such that predator identity might exert a strong influence on oyster populations. Likewise, oyster reef location, either as isolated patch reefs or saltmarsh-fringing reefs, can strongly influence the ecological processes impacting oyster populations. Therefore, this study sought to quantify the contribution of predator identity, in particular mesopredators, to oyster survival in the field, while also examining the role of landscape setting in predation. Using a multiple mesh size cage design, oyster survival was measured by excluding access to different groups of predators at both patch and fringing reef and reference sites in Hewlett’s Creek, Wilmington, North Carolina, in August/September 2013, while also monitoring settlement and recruitment at both reef locations from May to August 2013. The results indicated a significant cage by location interaction, indicating that the predator identity or modality was not the same across all sites. Despite this, at either reef location, oyster survival did not differ between 37-mm mesh cages, which allowed access only by mesopredators, and no-cage treatments, which allowed access to all predators, while survival was reduced by >20 % on fringing reefs relative to patch reefs. This study demonstrates the significant contribution of mesopredators, likely xanthid crabs, to oyster predation in the field at ambient predator densities and suggests that the differences in oyster abundance between patch and fringing reef locations are likely due to differential predation.