The rapid spread of Zika virus in the Americas and outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. We report a case of a 20-year-old pregnant woman from Salvador, Brazil whose fetus had developed hydrops fetalis, a condition where there is abnormal accumulation of fluid in the fetus, as well as severe central nervous system defects such as microcephaly and hydranencephaly. After fetal demise, ZIKV RNA was detected in central nervous system tissues and amniotic fluid. The case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes.