In a 3-year study, we examined landscape features (aspect, slope, sun exposure, canopy cover, type of ground cover, and nearest water source) that were potentially related to prevalence of infection with Plasmodium mexicanum in fence lizards (Sceloporus occidentalis) within a 4.5 ha study area in northern California, USA. Logistic regression analysis showed that ground cover type was the primary mediator of the probability of P. mexicanum infection. Infected lizards were captured more often in rock and/or leaf litter locations than in grassy ones. In another experiment, the study area was divided into 9 sites (0.07–0.33 ha), and infection prevalence was calculated for each. Three sites with high (>30%) infection prevalence had significantly more rocky outcrops and leaf litter than those with low (<20%) or moderate (20–30%) infection prevalence (N = 3 sites each). We conclude that lizard site selection may influence the probability of exposure to infected vectors and thus the likelihood of P. mexicanum infection. We also demonstrate that studies at different spatial scales may be required to understand fully the relationship between landscape features and parasite distribution.