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Shellfish fisheries and aquaculture within the Chesapeake Bay (hereafter 'the Bay') and its tributaries have been historically impacted by disease and climate events. Climate-driven shifts in temperature and salinity can alter host-parasite dynamics, influencing outbreaks. Here, we explore the relationship between temperature, salinity and parasite distribution and abundance in the eastern oysterCrassostrea virginica-Perkinsus marinussystem. We use long-term (30 yr) environmental data andP. marinussurveys in the Bay to identify (1) how climate affectsP. marinusprevalence and intensity, (2) seasonal and climate-driven infection patterns, and (3) regional environmental influences on disease. We found significant relationships betweenP. marinusinfection intensity, prevalence, increasing temperature and decreasing salinity. Our results indicated that there is an overall decreased abundance ofP. marinusprevalence and intensity throughout the Bay driven by decreases in salinity over time, most prominently from 2003-2020. However, these temporal trends in prevalence and intensity vary largely by region, with some regions still experiencing high disease burden. Examining monthly environmental parameters reinforced the dominant role of salinity in driving disease patterns. Salinity had significant relationships with prevalence and intensity year-round, with the largest effects in late spring/early summer. Monthly temperatures had fewer significant relationships to prevalence and intensity, but the largest significant effects were seen in late winter/early spring. Notably, this study is the first to document that winter salinity influences fall parasite prevalence, sometimes exerting a greater effect than temperature. Continued and expanded monitoring of marine disease is crucial to understand how the changing climate is impacting disease.