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COVID-19 represents the greatest health crisis in recent human history. To date, it is still difficult to estimate its impact on mortality. This paper investigates the excess crude mortality in 27 European countries. The differences between the values observed in 2020 and 2021 with those predicted by a joinpoint regression model were evaluated. A multi-regression analysis was implemented to assess the relationship between health variables and excess mortality. Europe experienced a marked and surprising (S-value > 52) increase in crude mortality during 2020 (Δ% = +10.0%, 95% CI: [2.5; 18.7]) and 2021 (Δ% = +12.1%, 95% CI: [4.3; 21.2]). The difference between average excesses of Eastern and Western countries was not surprising (S < 2) and had little relevance (ΔE-W = −2.4, 95% CI: [−2; 7]) during 2020 but was more pronounced (S = 15, ΔE-W = +17.2, 95% CI: [11.0; 23.5]) during 2021. Excess crude mortality increased in 2021 (Δ% = +65%, 95% CI: [12.6; 118], S = 5.9). Evidence has been found for a surprising and marked negative linear relationship between COVID-19 vaccinations and excess mortality ("2021 excess mortality = A + BX4", with "A = 58 ± 7, S = 28" and "B = −0.65 ± 0.10, S = 22, Radj2 = 0.65, 95% CI: [0.38; 0.82]). In light of the current literature, these findings provide solid evidence of the substantial role of COVID-19 in the unexpected and marked excess mortality recorded in Europe. COVID-19 vaccinations have appeared to be one of the main determinants for reducing mortality. Future research should explore these aspects in more detail. [ABSTRACT FROM AUTHOR]