Plant essential oils (EOs) are secondary metabolites derived from aromatic plants that are composed of complex mixtures of chemical constituents. EOs have been proposed as one of the alternative methods for bed bug (Cimex lectularius L.) control. In insecticide resistant mosquitoes and tobacco cutworm, EOs synergize pyrethroid toxicity by inhibiting detoxification enzymes. However, whether EOs and their constituents enhance pyrethroid toxicity in C. lectularius has remained unknown. Therefore, this study was designed to (i) determine the effects of binary mixtures of deltamethrin (a pyrethroid insecticide) with EOs or EO constituents or EcoRaider® (an EO-based product) on mortality of insecticide resistant and susceptible bed bugs, and (ii) evaluate the effects of EO constituent pre-treatment on detoxification enzyme activities of resistant and susceptible populations. Topical bioassays with binary mixtures of deltamethrin and individual EOs (e.g., thyme, oregano, clove, geranium or coriander oils) or their major constituents (e.g., thymol, carvacrol, eugenol, geraniol or linalool) or EcoRaider® at doses that kill approximately 25% of bed bugs caused significant increases in mortality of resistant bed bugs. However, in the susceptible population, only coriander oil, EcoRaider®, thymol, and carvacrol significantly increased the toxicity of deltamethrin. Detoxification enzyme assays with protein extracts from bed bugs pre-treated with EO constituents suggested selective inhibition of cytochrome P450 activity in the resistant population, but no impacts were observed on esterase and glutathione transferase activities in either population. Inhibition of P450 activity by EO constituents thus appears to be one of the mechanisms of deltamethrin toxicity enhancement in resistant bed bugs.