Sylvatic plague, caused by the flea-borne bacterium Yersinia pestis, is an invasive disease in North America that causes reductions of native fauna and transforms ecosystems. Fipronil baits have shown promise in reducing flea loads on prairie dogs Cynomys spp. for plague mitigation. Many species depend on prairie dogs and their ecological influences, including the black-footed ferret Mustela nigripes (ferret), an obligate predator of prairie dogs. To better understand how fipronil affects ferrets, we offered carcass portions from black-tailed prairie dogs C. ludovicianus that had consumed fipronil bait (0.005% fipronil by weight) to captive ferrets and monitored their health. We fed carcass portions of three prairie dogs to four adult ferrets for 1 week. No ill effects were observed in the ferrets. We collected scat from the ferrets before, during, and after their feeding on treated prairie dogs. We evaluated potential effects of ferret scat on larval fleas, which feed on organic matter. Fipronil residues were not detected in ferret scat samples collected before treatment. During and shortly after treatment, ferret scat contained 3.76 ng/g fipronil and 13.75 ng/g fipronil sulfone, on average, demonstrating trophic transfer of the residues from prey to predator. We presented 0.5 mg of ferret scat to each of 96 larval Oropsylla montana (Siphonaptera: Ceratophyllidae) and assessed survival rates over 24 h. When exposed to ferret scat lacking fipronil residues, 85% of larvae survived. Survival was reduced to 61% and 35% for larvae contacting or consuming scat with fipronil-residue, respectively. Fipronil residues in scat from a variety of species on prairie dog colonies, perhaps especially the prairie dogs, may assist in flea control and plague mitigation. Hosts eliminate fipronil residues, and fipronil residues in the environment degrade over time, reducing but not eliminating potential concerns with bioaccumulation.