Manaus, the capital of the Brazilian State of Amazonas, is the current epicenter of the COVID-19 epidemic in Amazonia. The sharp increase in deaths is a huge concern for health system administrators and society. The study aimed to analyze excess overall mortality according to Epidemiological Week (EW) in order to identify changes potentially associated with the epidemic in Manaus. Overall and cause-specific mortality data were obtained from the Central Database of the National Civil Registry and the Mortality Information System for 2018, 2019, and 2020. The study analyzed age bracket, sex, place of death, EW, calendar year, and causes of death. Ratios were calculated between deaths in 2019/2018 and 2020/2019 to estimate excess deaths, with 5% confidence intervals. No significant excess overall mortality was seen in the ratios for 2019/2018, independently of EW. Meanwhile, the ratios for 2020/2019 increased from 1.0 (95%CI: 0.9-1.3) in EW 11 to 4.6 (95%CI: 3.9-5.3) in EW 17. Excess overall mortality was observed with increasing age, especially in individuals 60 years or older, who accounted for 69.1% (95%CI: 66.8-71.4) of the deaths. The ratios for 2020/2019 for deaths at home or on public byways were 1.1 (95%CI: 0.7-1.8) in EW 12 and 7.8 (95%CI: 5.4-11.2) in EW 17. The explosion in overall mortality in Manaus and the high proportion of deaths at home or on public byways reveals the epidemic's severity in contexts of heavy social inequality and weak effectiveness of government policies, especially policies meant to deal with social inequalities and strengthen the Unified Health System.