Background: To control epidemic waves, it is important to know the susceptibility to SARS-CoV-2 and its evolution over time in relation to the control measures taken. Aim: To assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the first national lockdown in Belgium, we performed a nationwide seroprevalence study, stratified by age, sex and region using 3,000-4,000 residual samples during seven periods between 30 March and 17 October 2020. Methods: We analysed residual sera from ambulatory patients for IgG antibodies against the SARS-CoV-2 S1 protein with a semiquantitative commercial ELISA. Weighted seroprevalence (overall and by age category and sex) and seroincidence during seven consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity. Results: The weighted overall seroprevalence initially increased from 1.8% (95% credible interval (CrI): 1.0-2.6) to 5.3% (95% CrI: 4.2-6.4), implying a seroincidence of 3.4% (95% CrI: 2.4-4.6) between the first and second collection period over a period of 3 weeks during lockdown (start lockdown mid-March 2020). Thereafter, seroprevalence stabilised, however, significant decreases were observed when comparing the third with the fifth, sixth and seventh period, resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid-October 2020 a weighted overall seroprevalence of 4.2% (95% CrI: 3.1-5.2). Conclusion: During lockdown, an initially small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted. ; This work received funding from the European Union’s Horizon 2020 research and innovation program - project EpiPose (No 101003688), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 682540 TransMID), the Flemish ...