Hydrogen produced through water electrolysis or “Power-to-Hydrogen” can be used as a chemical molecule for heavy oil valorization, directly used as a fuel, or injected into the gas network. The natural gas network and the associated storage sites are important means of energy storage. Oxygen is also produced during electrolysis and can be upgraded. In this work, an experimental study focusing on PEM (Proton Exchange Membrane) electrolysis technology was carried out. The 70 kWe machine was able to produce up to 12 Nm3/h of hydrogen under nominal conditions (i.e. 42 kWt of hydrogen) at 99.9994 % purity level. The test rig includes all sub-systems generally found in a commercial machine. The aim was to find and describe empirical relationships between system variables and responses. These relationships were used to improve numerical model accuracy. In particular, the Design of Experiments (DOE) methodology was introduced and applied to electrolysis system assessment. Afterward, conclusions were drawn with regard to the strengths and weaknesses of this methodology when used to describe electrolysis system behavior.