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Abstract Since the COVID-19 outbreak, millions of people have been infected with SARS-CoV-2 around the world. An area of epidemiological relevance is Latin America, tropical regions, due to the distribution of endemic diseases such as chikungunya, dengue (DENV), malaria, Zika virus, where febrile disease abounds. The early signs and symptoms of DENV and COVID-19 could be similar, making it a risk that patients may be wrongly diagnosed early during the disease. The problem increases since COVID-19 infection can lead to false positives in DENV screening tests. We present two cases of acute undifferentiated febrile syndrome that were diagnosed with SARS-CoV-2 and DENV co-infection, confirmed by ELISA and RT-PCR for both viral pathogens. The occurrence of simultaneous or overlapped infections can alter the usual clinical course, severity, or outcome of each infection. Therefore, epidemiological surveillance and intensified preparation for those scenarios must be considered, as well as further studies should be done to address cases of co-infection promptly to avoid major complications and fatal outcomes during the current pandemic. Other endemic tropical diseases should not be neglected.