The World Health Organisation recommends monitoring the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated anti–SARS-CoV-2 total immunoglobulin (IgT) antibody seroprevalence and in vitro sero-neutralization in Nancy, France, in spring 2020. Individuals were randomly sampled from electoral lists and invited with household members over 5 years old to be tested for anti–SARS-CoV-2 (IgT, i.e., IgA/IgG/IgM) antibodies by ELISA (Bio-rad); the sero-neutralization activity was evaluated on Vero CCL-81 cells. Among 2006 individuals, the raw seroprevalence was 2.1% (95% confidence interval 1.5 to 2.9), was highest for 20- to 34-year-old participants (4.7% (2.3 to 8.4)), within than out of socially deprived area (2.5% vs. 1%, p = 0.02) and with than without intra-family infection (p < 10−6). Moreover, 25% of participants presented at least one COVID-19 symptom associated with SARS-CoV-2 positivity (p < 10−13), with highly discriminant anosmia or ageusia (odds ratio 27.8 [13.9 to 54.5]); 16.3% (6.8 to 30.7) of seropositive individuals were asymptomatic. Positive sero-neutralization was demonstrated in vitro for 31/43 seropositive subjects. Regarding the very low seroprevalence, a preventive effect of the lockdown in March 2020 can be assumed for the summer, but a second COVID-19 wave, as expected, could be subsequently observed in this poorly immunized population.