In Brazil, an epidemic of Zika virus (ZIKV) infections was declared in 2015 that coincided with alarming reports of microcephaly in newborns associated with mother infection. Although the virus has placental tropism, changes in the tissue morphology and immunity of infected patients have not yet been elucidated. Here, we investigated the histopathological and ultrastructural changes along with the immunological profile and the BDNF expression in rare placental material. Tissues were obtained in the 2015-2016 Brazilian epidemic, of ten ZIKV-infected patients during pregnancy, five resulting in cases of fetal microcephaly and five non-microcephaly, compared to five non-infected control placentae. Viral antigens were only detected in samples from the ZIKV infected patients. Infected placentae presented histopathological severe damage, while the ultrastructural evaluation showed abnormal organelles, such as clusters of virus-like particles consistent with the ZIKV dimensions. Increased infiltration of CD68+ and TCD8+ cells, expression of MMPs, cytokines (IFN-γ and TNF-α) and other immunological mediators (RANTES/CCL5 and VEGFR-2) confirmed excessive inflammation and vascular permeability dysfunction. An evaluation of BDNF showed a decrease that could modulate neuronal damage in the developing fetus. The placental changes caused by ZIKV are not pathognomonic, however, the data provide evidence that this infection leads to severe placental injury.