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Introduction: in 2019, the proliferation of a virus identified as SARS-CoV-2 emerged in the city of Wuhan, a district in China, quickly spread throughout the world, gaining pandemic status and less than 1 year, its repercussions and magnitude caused scientists, governments and society to adopt severe measures to combat this disease. Objective: to analyze mortality, incidence and mortality from COVID-19 in the municipalities of Botucatu and Serrana, São Paulo, Brazil. Methods: this is an ecological study with a time series design with secondary data. All registered cases and deaths registered by COVID-19 from April 2020 to August 2021 in the municipalities of Botucatu and Serrana, São Paulo, Brazil were considered. The incidence, mortality and lethality rate were used. The monthly and/or weekly percentage variation and their respective 95% confidence intervals were estimated. Results: it identified that 12.88% of the residents of the city of Botucatu were infected with COVID-19 and 8.61% of the population of the municipality of Serrana was infected. There was a stationary trend of mortality and incidence in the period between April 2020 and May 2021 and decreasing in both sexes in the mortality rate in the municipality of Serrana, in the city of Botucatu there was a trend of increasing mortality and incidence in the same period observed. Conclusion: The mass vaccination strategy of citizens in the cities of Botucatu and Serrana present robust data to consider that immunization has a decreasing effect on the number of cases and deaths from COVID-19, which effectively contributes to fighting the pandemic and reduces the contamination and progression of the disease to more severe cases.