The abiotic and biotic environments within which hosts and parasites interact influence disease dynamics. In our rapidly changing world, we must understand the mechanisms underlying such effects. In this study, we propose to explore how global change alters host immune function through changes in diet quality, and thereby dictates host tolerance and parasite virulence under future environmental conditions. We use the monarch butterfly, Danaus plexippus, and its protozoan parasite, Ophryocystis elektroscirrha (OE) to examine the effects of elevated CO2 (eCO2) on disease. Certain milkweed species contain high concentrations of particular cardenolides that, while weakly toxic to monarchs, confer increased tolerance to their parasites and decreased parasite virulence. Critically, eCO2 changes the cardenolide profiles and nutritional quality of milkweed foliage. We hypothesize that changes in milkweed chemistry (both medicinal and nutritional) under eCO2 influence monarch tolerance and OE virulence through effects on immune function. By utilizing novel chemical methods (1H-NMR-based plant metabolomics), we aim to relate changes in monarch immune responses to changes in food-plant chemistry induced by eCO2. We predict decreased immune function in monarchs feeding on milkweed with high cardenolide concentrations; monarchs that are nutrient-starved on eCO2 foliage will experience greater per unit toxicity of previously “medicinal” cardenolides.