In malaria-endemic regions, people often get exposed to various pathogens simultaneously, generating co-infection scenarios. In such scenarios, overlapping symptoms pose serious diagnostic challenges. The delayed diagnosis may lead to an increase in disease severity and catastrophic events. Recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected various areas globally, including malaria-endemic regions. The n Plasmodium and SARS-CoV-2 co-infection and its effect on health are yet unexplored. We present a case report of a previously healthy, middle-aged individual from the malaria-endemic area who suffered SARS-CoV-2 and n Plasmodium falciparum co-infection. The patient developed severe disease indications in a short time period. The patient showed neurological symptoms, altered hematological as well as liver-test parameters, and subsequent death in a narrow time span. We hereby discuss the various aspects of this case regarding treatment and hematological parameters. Further, we have put forward perspectives related to the mechanism behind severity and neurological symptoms in this fatal parasite-virus co-infection case. In malaria-endemic regions, due to overlapping symptoms, suspected COVID-19 patients should also be monitored for diagnosis of malaria without any delay. The SARS-CoV-2 and n Plasmodium co-infection could increase the disease severity in a short time span. In treatment, dexamethasone may not help in severe cases having malaria as well as COVID-19 positive status and needs further exploration.n “,”In malaria-endemic regions, people often get exposed to various pathogens simultaneously, generating co-infection scenarios. In such scenarios, overlapping symptoms pose serious diagnostic challenges. The delayed diagnosis may lead to an increase in disease severity and catastrophic events. Recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected various areas globally, including malaria-endemic regions. The n Plasmodium and SARS-CoV-2 co-infection and its effect on health are yet unexplored. We present a case report of a previously healthy, middle-aged individual from the malaria-endemic area who suffered SARS-CoV-2 and n Plasmodium falciparum co-infection. The patient developed severe disease indications in a short time period. The patient showed neurological symptoms, altered hematological as well as liver-test parameters, and subsequent death in a narrow time span. We hereby discuss the various aspects of this case regarding treatment and hematological parameters. Further, we have put forward perspectives related to the mechanism behind severity and neurological symptoms in this fatal parasite-virus co-infection case. In malaria-endemic regions, due to overlapping symptoms, suspected COVID-19 patients should also be monitored for diagnosis of malaria without any delay. The SARS-CoV-2 and n Plasmodium co-infection could increase the disease severity in a short time span. In treatment, dexamethasone may not help in severe cases having malaria as well as COVID-19 positive status and needs further exploration.n