Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, leading to the coronavirus disease 2019 (COVID-19) pandemic. Because a significant proportion of the COVID-19 confirmed cases were concentrated in the capital metropolitan area of South Korea, and a large proportion of the population in the area had been adequately vaccinated against COVID-19, we conducted a seroprevalence surveillance study focusing on the residents of the capital metropolitan area in South Korea. Methods: We used a quota-sampling method to obtain blood samples from 1,000 individuals per round, equally stratified across seven age categories and sexes and regions, from five medical institutions located within the capital metropolitan area of South Korea. During five consecutive months (rounds) between January 2022 and May 2022, a total of 5,000 samples were analyzed for anti-spike (S) and anti-nucleocapsid (N) antibodies. Results: High anti-S seropositivity was observed in all age groups, which corresponded to the vaccine coverage during the study period. Both the cumulative incidence based on polymerase chain reaction (PCR) and the estimated seroprevalence based on anti-N seropositivity increased in the fourth and fifth rounds, which corresponded to April 2022 and May 2022. Seroprevalence coincided with the cumulative incidence during the first three rounds, but exceeded from the fourth survey onwards when infection with omicron variants was increased rapidly in Korea. Conclusion Seroprevalence confirmed the number of infection cases outside of PCR testing-based surveillance. Seroepidemiological surveillance can help us understand vaccine responses and detect hidden infections, thereby providing appropriate public health guidance for achieving population-level immunity.