The effects of parasites on their hosts can vary among host populations, but few studies have examined geographic variation in host-parasite interactions. We examined the effects of Capillaria hepatica (Nematoda) infection on deer mice (Peromyscus maniculatus gracilis) from two different populations. Specifically, we measured the basal metabolic rate (BMR), cold-stress maximum oxygen consumption (MR peak), metabolic scope (MR peak/BMR) and thermogenic endurance of infected and uninfected mice from one population with, and a second population without, a history with C. hepatica. Infection had no effect on BMR, but did have effect on cold-stress measures. A previous study documented a significant relationship between survival and MR peak in wild deer mice; hence, the effects of infection on the parameters that we measured could influence fitness. Only mice that had no historical association with C. hepatica displayed negative consequences of infection, which suggests that the historical host population has evolved mechanisms to cope with infection. Models of the evolution of virulence should include evolutionary responses of both hosts and parasites, particularly when systems involve macroparasites that have long generation times.