The growing concern about Greenhouse Gas (GHG) emissions led institutions to further reduce the limits on vehicle-related CO2 emissions. Therefore, car manufacturers are developing vehicles with low environmental impact, like Hybrid-Electric Vehicles (HEVs), which in the series architecture employ an Internal Combustion Engine (ICE) coupled with an electric generator for battery recharging, thus extending the range of a Battery Electric Vehicle (BEV). For this kind of application, small four-stroke Spark Ignition (SI) engines are preferred, as they are a proven and reliable solution to increase the driving range with very low environmental impact. In series hybrid-electric powertrains, the ICE is decoupled from the drive wheels, then it can operate in a steady-state high-efficiency working point, regardless of the power required by the mission profile. The benefits of lean combustion can be exploited to increase efficiency and reduce CO2 and NOx emissions. This work analyzes the energy consumption and pollutant emissions of a series-HEV equipped with a hydrogen-fueled SI engine. Hydrogen fueling promotes faster flame development and propagation, thus improving the combustion stability also under lean mixtures, with benefits on fuel consumption and emissions. The effects of the lean-burn operation on engine combustion and NOx emissions are investigated by a 1-D engine model, validated against experimental measurements at the test bench. Based on 1-D simulation results, the benefits of high-efficiency engine operation on a series-HEV in terms of energy consumption and NOx emissions are assessed by vehicle model simulations on different driving scenarios. The main purpose of vehicle simulations is to evaluate the best compromise between battery pack downsizing, charging power, and energy consumption for a fixed target vehicle driving range.