Background Monitoring changes of seroprevalence over time is important at the beginning and during of COVID-19 outbreak to anticipate its dynamics and plan an adequate public health response. Methods We conducted a repeated cross-sectional investigation among asymptomatic outpatient subjects and covered 0.1% of total population of Northern Serbia (Autonomous Province of Vojvodina). Each participant was tested for anti-SARS-CoV-2 antibodies using an immunochromatographic qualitative test (point-of-care rapid test). In the last round of survey IgG antibodies targeting the S1 subunit of the spike protein and the nucleocapsid protein of SARS-CoV-2 virus were assessed. Results During the four rounds of survey (between the end of April and the end of September), anti-SARS-CoV-2 seropositivities based on immunochromatographic test results were 2.60% (95% CI 1.80–3.63), 3.93% (95% CI 2.85–5.28), 6.11% (95% CI 4.72–7.77) and 14.60% (95% 12.51–16.89), respectively. After adjusting with results obtained from the Line immunoassay test, the estimated overall seroprevalence increased to 16.67% (95% CI 14.45–19.08) corresponding to 322,033 infections in total by the end of September 2020 in Vojvodina’s population. Throughout the course of the study, for every RT-PCR confirmed case of COVID-19, there were 39–87 additional infections in Vojvodina. No significant difference (p>0.05) in SARS-CoV-2 seropositivity regarding gender and between age subgroups was observed over the course of the survey. Conclusions The population prevalence of SARS-CoV-2 antibodies implies much more widespread infection in Vojvodina than indicated by the number of confirmed cases. However, our results suggest that the population of Vojvodina has not reached a desirable level of protection from SARS-CoV-2 virus by the end of September 2020.