Infectious disease threats are increasingly recognized as a major contributor to mortality in wild populations of African wild dog (Lycaon pictus, AWD). Canine distemper virus (CDV) infection has been implicated as a cause of pack mortality in both captive and wild AWD populations. Ten animals were vaccinated with RecombitekTM C3, a vaccine containing a recombinant CDV, and modified live canine parvovirus (CPV) and adenovirus-2 components, at 8, 12, and 16 wk of age. Half of the pups received the vaccine IM and the other half SC. All ten pups had a positive serological response to CDV after the second vaccination, which decreased or stagnated after the third vaccination. Half of the pups had CDV titers ≥32 at 20 wk of age. Titers to CPV were high in all pups prior to vaccination and dropped precipitously over the course of the vaccine series. At the last sampling period, only 50% of the pups had measurable CPV titers. An initially higher titer was seen for CDV in the IM administration group; however, this was not significant at later time points. Vaccination with Recombitek C3 appears to be safe and effected a sustained serological response to CDV in AWD.