To bridge the gap between oxygen reduction electrocatalysts development and their implementation in real proton exchange membrane fuel cell electrodes, an important aspect to be understood is the interaction between the carbon support, the active sites, and the proton conductive ionomer as it greatly affects the local transportations to the catalyst surface. Here we show that three Pt/C catalysts, synthesized using the polyol method with different carbon supports (low surface area Vulcan, high surface area Ketjenblack, and biomass-derived highly ordered mesoporous carbon), revealed significant variations in ionomer-catalyst interactions. The Pt/C catalysts supported on ordered mesoporous carbon derived from biomass showed the best performance under the gas diffusion electrode configuration. Through a unique approach of operando X-ray Absorption Spectroscopy combined with gas sorption analysis, we were able to demonstrate the beneficial effect of mesopore presence for optimal ionomer-catalyst interaction at both molecular and structural level.