Mosquitoes represent a major source of disease transmission and possess the uncanny ability to locate suitable animal-hosts, a feature mediated by their exquisite olfactory system. Insect repellents such as N,N-Diethyl-meta-toluamide, also called DEET, have been shown to activate and inhibit mosquito odorant receptors, resulting in behavioral modulation. This and other repellents available for personal protection against mosquitoes are topically applied on the skin and operate at a short range. In our search for potential long-range odorant repellents, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former the ability to block odorant receptor function and inhibit human-host attraction. Using the two-electrode voltage clamp of Xenopus laevis oocytes as a pharmacological platform, we provide evidence that indole inhibits the Aedes aegypti (R)-1-octen-3-ol receptor OR8, a receptor involved in the decision of female mosquitoes to identify human hosts. Coincidentally, behavioral experiments in an arm-in-cage and flight tunnel assays suggest that indole inhibits animal-host seeking behavior in female Aedes aegypti. Together, our findings suggest that indole may be a candidate spatial repellent for the long-range protection of humans against mosquito bites.