Objectives: The COVID-19 pandemic is due to SARS-CoV-2 coronavirus infections. It swept across the world in the spring of 2020, and so far it has caused a huge number of hospitalizations and deaths. In the present study, the authors investigated serum anti-SARS-CoV-2 antibody prevalence in the period of June 1–September 25, 2020, in 7561 subjects in Modena, Northern Italy. Material and Methods: The study population included 5454 workers referred to testing by their companies, and 2107 residents in the Modena area who accessed testing through self-referral. Results: The authors found the overall seroprevalence to be 4.7% (95% confidence interval [CI] 4.2–5.2%), which was higher in women (5.4%, 95% CI: 4.5–6.2%) than in men (4.3%, 95% CI: 3.7–4.9%), and in the oldest age groups (7.3%, 95% CI: 5.2–9.3% for persons aged 60–69 years, and 11.8%, 95% CI: 8.6–15.1%, for persons aged ≥70 years). Among the occupational categories, the highest seroprevalence was found in healthcare workers (8.8%, 95% CI: 7.0–10.5%), dealers and vehicle repairers (5.2%, 95% CI: 2.9–7.6%), and workers in the sports sector (4.0%, 95% CI: 1.8–6.1%), while there was little or no such evidence for those employed in sectors such as transport and storage, accommodation and restaurant services, and the school system. Conclusions: These results have allowed, for the first time, to assess population seroprevalence in this area of Italy severely hit by the epidemic, while at the same time identifying the subgroups at a higher risk of exposure to SARS-CoV-2. Int J Occup Med Environ Health. 2022;35(1):63–74