Because recent studies have not demonstrated a strong relationship between rodent density and Sin Nombre virus (SNV) seroprevalence, there is speculation that seroprevalence may be related to other factors, including habitat quality and food availability. We evaluated densities of deer mice (Peromyscus maniculatus), plant cover and biomass, and terrestrial arthropod biomass at 2 sites in the southwestern United States to identify factors that may affect the seroprevalence rate of SNV within a rodent population. Seroprevalence differed significantly between years. Although interaction of deer-mouse density, plant cover and biomass, and arthropod biomass was not a strong predictor of seroprevalence (R² = 0.64, P = 0.04), we observed a significant contribution to a repeated-measures model by deer-mouse density (P = 0.02). Our data suggest that as rodent density increases, so does the seroprevalence rate within that population. Although not significantly correlated, we observed the lowest levels of arthropod biomass when seroprevalence was highest. Based on our results, evaluating changes in habitat quality and incorporating measurement of local ecological variables with studies of fluctuations in rodent density may aid in predicting human outbreaks of hantavirus disease.