Background: Senegal reported the first COVID-19 case on March 2, 2020. A nationwide cross-sectional epidemiological survey was conducted to capture the true extent of COVID-19 exposure. Methods: Multi-stage random cluster sampling of households was carried out between October 24 and November 26, 2020, at the end of the first wave of COVID-19 transmission. Anti-SARS-CoV-2 antibodies (IgG and/or IgM) were screened using three distinct ELISA assays. Adjusted prevalence for the survey design were calculated for each test separately, and thereafter combined. Crude, adjusted prevalence based on tests performances and weighted prevalence by sex-age strata were estimated to assess the seroprevalence. Findings: Of the 1,463 participants included in this study, 58·8% were women and the mean age of participants was 29·2 years (range 0·25–82·0). The national seroprevalence was estimated at 28 . 4% (95% CI: 26·1-30·8). There was substantial regional variability. Four regions recorded the highest seroprevalence: Ziguinchor (56·7%), Sedhiou (48·0%), Dakar (44·0%) and Kaolack (32·7%) whereas, Louga (11·1%) and Matam (11·2%), located in the Center-North, were less impacted in our analysis. All age groups were impacted and the prevalence of SARS-CoV-2 was comparable in symptomatic and asymptomatic groups. We estimated 4,744,392 SARS-CoV-2 (95% CI: 4,360,164 – 5,145,327) potential infected in Senegal compared to 16,089 COVID-19 RT-PCR laboratory-confirmed cases reported at the time of the survey. Interpretation: These results provide an estimate of SARS-CoV-2 virus dissemination in the Senegalese population. Preventive and control measures need to be reinforced in the country and especially in the south border regions. Funding Information: This work was supported by US Centers for Disease Control and Prevention (CDC), the Senegalese Ministry of Health, the Senegalese National Statistics and Demography Agency (ANSD), the WHO Unity program and the COVID-19 Task-force of the International Pasteur Institute Network (IPIN, REPAIR project). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: All participants have consented to participate in the study. For people younger than 18 years, a legal representative provided informed consent. The study was approved by the Senegalese National Ethics Committee for Research in Health (reference number N°0176/MSAS/DPRS/CNERS, 10 October 2020).