This study seeks to find the correlation between case fatality rates (CFRs) and third-dose vaccination coverage in 244 counties (si/gun/gu) of South Korea during the omicron variant wave. Multivariate regression analyses report that the higher third-dose vaccination rates were correlated with lower regional CFRs, when controlling for age structure. If the thirddose vaccination rate of a county is higher by 10%, it would have a CFR lower by 0.05% (95% confidence interval, 0.03–0.08%). As the number of cumulative confirmed cases in South Korea was 16,353,495 as of April 20, 2022, a lower CFR by 0.03–0.08% is equivalent to 4,394–12,448 lives (8.6–24.4 per 100,000) spared. County-specific characteristics, such as age structure, intensive care unit availability, and the level of non-pharmaceutical interventions may also affect the extent of this correlation. The conclusion implicates the potential role of coronavirus disease 2019 vaccines in reducing the pressure on the regional healthcare capacity.