Background and Objective: Wastewater-Based Epidemiology (WBE) is a complementary approach to laboratory-based surveillance for monitoring SARS-CoV-2 circulation and variants, as well as an early warning system for possible new outbreaks. Following Recommendation (EU) 2021/472, since October 2021, a systematic environmental surveillance of SARS-CoV-2 has been activated in Italy. For the Piemonte Region, the study aimed to track virus circulation in local wastewater and evaluate the relationship to COVID-19 cases. Methods: Raw wastewater samples (n=424) from 6 wastewater treatment plants (WWTPs) covering 44% of the regional population were concentrated via polyethylene glycol precipitation, and viral RNA was quantified by RT-qPCR targeting ORF1b-nsp14. Weekly SARS-CoV-2 concentrations in wastewater were compared with the prevalence rates per 1,000 inhabitants of COVID-19 positive subjects in the WWTPs catchment areas. Results: Viral RNA was detected in 96.9% of the samples, with concentrations ranging from 4.4×103 to 1.6×107 genome copies/ (die*equivalent inhabitant). For the period December 2021-January 2022, an increase in the SARS-CoV-2 RNA concentration in wastewater was observed with a clear advance of about 7 days compared to the prevalent cases. In general, good agreement was found between environmental data and prevalent cases during the observation period, even during periods of low prevalence (< 25 cases per 1000 population). Conclusions: WBE has the potential to effectively integrate laboratory-based and syndromic surveillance because of its ability to describe spatial and temporal trends of COVID-19 at the population level in near-real time. A study is underway to develop a more reliable correlation model with clinical data to make WBE a possible driver for public health decisions. The activities of the SARI network are conducted with the financial support of the Italian Government (Decreto Legge 25.05.2021 n. 73), of Ministry of Health (Program CCM2020) and of EU Commission, DG ENV (Grant Agreement 060701/2021/864481/SUB/ENV.C2).