A common method of estimating natural mortality in bivalves includes several assumptions that are likely violated for oysters Crassostrea virginica in Chesapeake Bay, Maryland. In addition, while oyster disease dynamics are well studied spatially and temporally in the mid-Atlantic region, changes in disease-related relationships have not been investigated in Maryland. We developed a Bayesian estimator for natural mortality and applied it to oysters in Maryland. We then used the model output along with environmental factors and disease data to explore changes in the disease system over time. We found the largest differences in natural mortality estimates between the box count method and Bayesian model 1-3 years after a high mortality event. Some relationships changed over time in the disease system, most notably those associated with MSX, suggesting resistance to MSX has potentially developed. This work improves our estimates of natural mortality and understanding of oyster disease dynamics in Maryland.