Host fitness is reduced by parasites, and hence parasites often are influential agents of natural selection. Traits that confer parasite resistance typically have significant genetic variation, which may be maintained if host fitness is reduced by resistance when parasites are absent. To test for costs associated with resistance, we examined interactions between parasitic mites, Gamasodes queeslandicus, in the host, Drosophila melanogaster. Selection for resistance increased the ability of flies to prevent mite infestation. Differential gene expression profiling revealed that ectoparasite resistance altered transcript expression patterns associated with metabolic processes. These expression differences were supported by decreased starvation resistance, likely arising from increased utilization of nutrient reserves by selected flies. Behavioral activity of the selected flies was increased during the night, which yielded increased nighttime oxygen consumption. Substantial day and night movement of G. queeslandicus mites was noted, suggesting increased resistance could be from increased fly activity during the night when flies would normally be least active. Importantly, flies that were restrained showed no increase in resistance, highlighting that movement is a critical factor in behavioral resistance to the ectoparasitic mite. Our studies provide evidence that ectoparasite resistance imposes costs in the absence of mites, manifested as increased host metabolism and activity at night, leading to decreased starvation resistance.