Zika virus has emerged in the Americas, where dengue virus is endemic. Among the 4 serotypes of dengue virus, antibody-dependent enhancement is thought to enhance viral replication and disease severity. Reports suggest that anti–dengue virus antibody may enhance Zika virus replication. We investigated whether Zika virus antibodies enhance dengue virus replication, by exposing C57Bl/6 mice to Zika virus. Polyclonal serum was verified for strong Zika virus–neutralizing, dengue virus–subneutralizing capacity. Then we determined the enhancement capabilities of Zika virus–immune serum for dengue virus in vitro. We showed that Zika virus antibodies have the ability to enhance dengue virus infections, which is important, because in many Zika virus–affected areas, dengue virus is expected to remain endemic.