Parasites can shape population, community, and ecosystem dynamics, especially if their hosts play a key role in the ecosystem. Multiple parasites frequently co-infect hosts that alter disease dynamics via a variety of mechanisms. Further, abiotic and biotic factors often differentially affect hosts and their associated parasites, with direct and/or indirect effects on disease prevalence and intensity. We conducted a field survey of eastern oyster Crassostrea virginica populations in the northern Gulf of Mexico to examine spatial patterns in parasite species richness of this foundation species. We assessed whether environmental factors and/or host characteristics best predicted prevalence and intensity of the most common micro- (Perkinsus marinus; Dermo) and macro-parasites (boring sponges Cliona spp., mud blister worms Polydora websteri) in the region. The number of parasite species infecting each host (i.e. species richness) was spatially homogeneous due to variation in the predominant factors underlying the prevalence and intensity of each species. These factors were host density, tidal elevation, and temperature for Dermo; tidal elevation and host size for boring sponges; and salinity for mud blister worms. Host condition depended on abiotic and biotic factors, including tidal elevation (intertidal > subtidal) and prevalence of both Dermo (positive relationship) and boring sponges (negative relationship). Abiotic influences on oysters and parasites, and multiple parasite effects, produced an unexpected positive correlation between host condition and Dermo prevalence. Thus, predicting the likelihood of disease outbreaks and assessing the long-term health of host populations requires consideration of the combined effects of multiple parasites, abiotic conditions, and biotic factors.