The previous works on the use of PEM Fuel Cell based power supply system for the operation of off-grid RBS (Radio Base Stations) sites showed a strong influence of system design parameters on the energy conversion performance. In this paper a perturbation of system design is studied with validated models to understand the variability of performance over a full year operation. Moreover, a multi-objective optimal sizing methodology is proposed in terms of the minimization of a functional parameter taking into account costs, RES (Renewable Energy Sources) exploitation and pollutant emission factors. The influence of different weather conditions on the HRES (Hybrid Renewable Energy Systems) performance is analyzed investigating the system behavior for three different locations in Europe. The analysis of three real case studies showed that 20% ratio of the energy produced by fossil fuels over the energy produced by renewables sources can be obtained slightly increasing the PV (PhotoVoltaic) plant size with minor effects on the RES exploitation. Moreover, a lower LCOE (Levelized Cost Of Energy) can be achieved increasing the PV size and reducing battery size with an unavoidable reduction of the RES exploitation. Results for different sites highlighted the obtainment of different optimal sizings for each site. However, similar performance parameters can be obtained in the different case studies for Tilos, Rome and Brighton with an average LCOE of 0.5 €/kWh and a variability in the order of 0.1 €/kWh.