Protozoal meningoencephalitis, caused by Toxoplasma gondii and Sarcocystis neurona, represents a significant cause of mortality for reproductive-aged sea otters. Individual and behavioral risk factors for T. gondii exposure include male sex, and diet preferences including a high percentage of kelp snails. The only known definitive hosts shedding infectious oocysts are terrestrial felids, but despite this, little is known about features of the terrestrial environment that determine risk of pathogen transfer into the marine environment. In this study we present a novel method for evaluating the relationship between landscape-based features and disease exposure risk. We conducted a spatially-weighted regression using a weighting index calculated from discharge of each river within the study area and distances between capture location and river outflows. Distances were calculated based on real-world coastal topography to reflect the distance an otter must swim between two points. This index was used to weight exposure of each study animal to indices of development and land-cover, calculated for coastal watersheds adjacent to the entire sea otter range in California as well as comparison sites in Washington and Alaska. While a simple comparison of the features of the study sites with seroprevalence indicated a positive association with some land-cover categories (cropping - spearman’s ρ= 0.9, p = 0.0001; pasture - ρ= 0.72, p = 0.01), weighted regression analysis found these factors to be less accurate predictors of serum antibody status than human housing unit density. A 2-fold increase in housing density in adjacent watersheds was associated with a 1.3-fold increase in disease exposure odds among sea otters (p<0.0001). We conclude that specific features of areas of denser human habitation are conducive to greater oocyst loading or mobilization into freshwater. This effect may be driven by increased definitive host abundance in areas of human habitation or altered watershed permeability.