Introduction The COVID-19 pandemic has highlighted social inequalities in health. In March 2020, numerous cases were reported in three disadvantaged neighborhoods of the city of Perpignan, in southern France, home to a large Romani community. A seroprevalence study was conducted in July to assess the level of infection in these neighborhoods following the first wave and to identify factors associated with seropositivity. Method The SCoPe study is a cross-sectional survey conducted among the population aged 6 years and older in three neighborhoods of Perpignan. Homes were selected using systematic sampling, and participants were selected at random. Participants’ blood samples were analyzed using the EIecsys Anti-SARS-CoV-2 test. Seroprevalence was estimated based on adjusted data, and associated risk factors were identified using a logistic regression model. Results The seroprevalence of anti-SARS-CoV-2 antibodies was 35.4% (95% CI: 30.2–41.0), with significant variations by neighborhood (13.9% to 46.7%). Individuals aged 15 to 64 had a higher risk of being seropositive compared to those aged 65 and older. The prevalence of obesity was 40.7% (35.8–45.8), and obese individuals were more likely to be seropositive (aOR = 2.0 [1.1–3.8]). The presence of clinical cases within the family increased the risk of being HIV-positive (one case versus none: ORa=2.5 [1.3–5.0]). In the most affected neighborhood, the risk of being seropositive was higher for people living in a 1-2 room dwelling versus a 4-room dwelling (ORa=2.8 [1.2-6.3]). Working during lockdown was associated with a lower probability of seropositivity (ORa=0.2 [0.03-1.0]). Discussion SARS-CoV-2 transmission was significant in this vulnerable population. These results underscore the need to strengthen and adapt prevention measures, taking into account all social determinants of health, particularly housing conditions.