Dengue is an increasing threat to individuals living in or visiting endemic countries. Effective vaccines have become available, but their use in travelers is typically only recommended to individuals with documented prior infection. We present a fatal case of severe dengue in an unvaccinated traveler without known prior dengue virus infection but longitudinal serologic and molecular evidence for secondary infection. In the context of this case and vaccination guidance for travelers, we discuss pre-vaccination screening, potential implications for travelers to regions with ongoing outbreaks, and emphasize the importance of serostatus-independent vaccines.