In this work, an approach is developed to study the seismicity associated with the impoundment and level changes of a water reservoir (reservoir induced seismicity – RIS). The proposed methodology features a combination of a semi-analytical poroelastic model with an earthquake nucleation approach based on rate-and-state frictional law. The combined approach was applied to the case of the Pertusillo Lake, located in the Val d’Agri area (Italy), whose large seasonal water level changes are believed to induce protracted micro-seismicity (local magnitude ML < 3). Results show that the lake impoundment in 1962 could have produced up to 0.5 bar (1 bar = 100 kPa) changes in Coulomb failure stress (ΔCFS), while the seasonal water level variation is responsible for variation up to 0.05 bar. Modeling results of the seismicity rates in 2001−2014 show that the observed earthquakes are well correlated with the modeled ΔCFS. Finally, the reason that the seismicity is only observed at southwest of the Pertusillo Lake is provided, which is likely attributed to different rock lithologies and depletion caused by significant hydrocarbon exploitation in the northeastern sector of the lake.