Background In the first weeks of the COVID-19 epidemic in Belgium, a repetitive national serum collection was set up to monitor age-related exposure through emerging SARS-CoV-2 antibodies. First objective was to estimate the baseline seroprevalence and seroincidence using serial survey data that covered the start of a national lock-down period installed soon after the epidemic was recognized. Methods A prospective serial cross-sectional seroprevalence study, stratified by age, sex and region, started with two collections in April 2020. In residual sera taken outside hospitals and collected by diagnostic laboratories, IgG antibodies against S1 proteins of SARS-CoV-2 were measured with a semi-quantitative commercial ELISA. Seropositivity (cumulative, by age category and sex) and seroincidence over a 3 weeks period were estimated for the Belgian population. Findings In the first collection, IgG antibodies were detected in 100 out of 3910 samples, whereas in the second collection 193 out of 3391 samples were IgG positive. The weighted overall seroprevalence increased from 2.9% (95% CI 2.3 to 3.6) to 6.0% (95% CI 5.1 to 7.1), reflected in a seroincidence estimate of 3.1% (95% CI 1.9 to 4.3). Age-specific seroprevalence significantly increased in the age categories 20-30, 80-90 and ≥90. No significant sex effect was observed. Interpretation During the start of epidemic mitigation by lockdown, a small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2. Funding This independent researcher-initiated study acknowledges financial support from the Antwerp University Fund, the Flemish Research Fund, and European Horizon 2020.