A controlled clinical trial was carried out to assess the adulticidal and anti-feeding effectiveness of a spot-on combining fipronil and permethrin (Effitix, Virbac, Carros, France) in preventing Culex pipiens from feeding on dogs. Twelve dogs with equal sensitivity to mosquitoes were included in the study and divided into two groups of six dogs: an untreated control group and a group treated with Effitix. All dogs were challenged with 80 females C. pipiens for 90 ± 5 min on days -7, 1, 7, 14, 21, and 28 (day 0 being treatment day). The number of engorged, dead, and live mosquitoes was determined after each exposure to treated and untreated dogs. Dead mosquitoes were also counted 24 h after exposure. The anti-feeding effect of the spot-on formulation was 100, 99.5, 97.7, 98.3, and 96.7% on days 1, 7, 14, 21, and 28, respectively. The mortality effect was 66.6, 55.9, 38, 17.2, and 12.3% on days 1, 7, 14, 21, and 28, respectively. At each challenge point, the mortality and anti-feeding effects on mosquitoes were significantly different between the control and treated group (p < 0.05). The results indicate that a combination of permethrin and fipronil could be used as an effective mosquito control strategy in dogs and is therefore recommended for use in a dirofilariasis prevention program.