The costs of chemical sequestration in Lepidoptera larvae are largely unknown. In this study, we attempt to quantify the physiological costs of iridoid glycoside sequestration in the Buckeye caterpillar, Junonia coenia. We hypothesize that increased iridoid glycoside concentration in plants will lead to lower immune response due to physiological costs involved in the sequestration process. We measured encapsulation and melanization of silica beads (proxy for a parasitoid egg) injected into buckeye caterpillars feeding on high and low diets of iridoid glycosides. In addition, we measured the respiration response of these caterpillars feeding on the experimental diets using a CO2 gas analyzer. Results showed that caterpillars feeding on diets with high concentrations of iridoid glycosides had a lower immune response and a higher respiration response, indicating a physiological cost to sequestration. We conclude that caterpillars that are chemically defended against generalist predators such as spiders and ants may be more vulnerable to more specialized predators like parasitoids due to a compromised immune system.