Human bed bug infestations have undergone a recent global resurgence. The human antiparasitic drug ivermectin has been proposed as a strategy to help control bed bug infestations, but in vivo data are lacking. We allowed separate populations of the common bed bug, Cimex lectularius L., to feed once on a rabbit before and after it was injected subcutaneously with 0.3 mg/kg of ivermectin, and bed bug morbidity and mortality were recorded. Ivermectin levels in the rabbit were measured using high-performance liquid chromatography and mass spectroscopy. Ivermectin blood levels of ∼2 ng/mL caused reductions in bed bug fecundity, and levels of >8 ng/mL caused bed bug death and long-term morbidity including reductions in refeeding, mobility, reproduction, and molting. Gut bacterial cultures from the fed bed bugs showed that ivermectin altered the bed bug gut microbiome.