The nascent stages of speciation start with the emergence of sexual isolation. Understanding the influence of reproductive barriers in this evolutionary process is an ongoing effort. We present a study of Drosophila melanogaster admixed populations from the southeast United States and the Caribbean islands known to be a secondary contact zone of European- and African-derived populations undergoing incipient sexual isolation. The existence of premating reproductive barriers has been previously established, but these types of barriers are not the only source shaping sexual isolation. To assess the influence of postmating barriers, we investigated putative postmating barriers of female remating and egg-laying behavior, as well as hatchability of eggs laid and female longevity after mating. In the central region of our putative hybrid zone of American and Caribbean populations, we observed lower hatchability of eggs laid accompanied by increased resistance to harm after mating to less-related males. These results illustrate that postmating reproductive barriers act alongside premating barriers and genetic admixture such as hybrid incompatibilities and influence early phases of sexual isolation.