Introduction: Caused by SARS-CoV-2, COVID-19 generates respiratory infections ranging from asymptomatic to severe and lethal forms. In the state of Piauí, the first confirmed case and the first death occurred in March, and since then the State has sought to increase strategic plans in order to avoid an increase in mortality, with the aim of the present study to analyze the epidemiological profile of deaths by COVID-19 in Piauí. Method: This is a retrospective observational study on the epidemiological profile of cases of death from COVID-19 in the State of Piauí until the end of December 2020. Results: At the end of 2020, Piauí registered a total of 2,841 accumulated deaths, the majority of which were reported in people of the male sex, with a predominance among the 61 to 80 age groups. 87.35% of these cases had comorbidities, mostly arterial hypertension or cardiovascular diseases. Implications: The state of Piauí demonstrates an epidemiological profile of its deaths similar to other cities, but this is not synonymous with disease control. Public policies must continue and measures must be intensified to avoid aggravating the situation.