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Oropouche virus (OROV) is an arbovirus transmitted to humans by mosquitoes, with the Culicoides paraensis mosquito species as its primary vector, causing Oropouche fever. Records of an outbreak in Brazil have so far been restricted to Central-North region of the country. However, an increase in the occurrence of cases of this disease has been observed in the state of Bahia, where the rapid spread of the OROV virus is configured as an outbreak in the South and East macro-regions of great concern for public health. This is a case-based study of acute OROV infection that led to the death of two young women without comorbidities amid an outbreak of the disease. The patient’s biological samples were subjected to routine real-time PCR assays for the diagnosis of Oropouche fever and other pathologies. In addition, serological tests and metagenomics were performed during the laboratory investigation. This study shows the need for an active and efficient surveillance system to control the spread of this virus, as well as the importance of carrying out prospective studies to better clarify the natural history of this disease.