BACKGROUND: We aimed to estimate the SARS-CoV-2 antigen and antibody seroprevalence in one of the worst-affected by the pandemic semi-closed communities in Greece, Deskati, and evaluate the sociodemographic and clinical correlations of functional antibody responses. METHODS: The Ag2019n-CoV V1310/V1330 Rapid Test (Prognosis Biotech, Greece) was used for antigen detection. The Rapid Test 2019-nCoV Total Ig, V1210/V1230 (Prognosis Biotech, Greece), and the SARS-CoV-2 IgG II Quant method (Architect, Abbott, Illinois, USA) were used for antibody testing. RESULTS: None of the participants had a positive antigen result. SARS-CoV-2 seropositivity ranged from 13% to 45% in the study population, depending on the method. One-third of the participants with known past infection had a positive antibody test result 77 +/- 13 days after infection. Two-fifths of infections determined by serology were asymptomatic. The advancing age and hospitalization predicted seropositivity among patients with past infection. Half of the participants who tested positive for antibodies were not aware of past infection. CONCLUSIONS: High-burden contexts in Greece, such as Deskati, are not so far from herd immunity thresholds. We highlighted the value of low-cost serosurveys targeting both symptomatic and asymptomatic populations to evaluate the natural immune response to SARS-CoV-2 in nonvaccinated susceptibles and design evidence-based policies for lifting lockdowns.