AbstractThe role of the perovskite lattice oxygen in the oxygen evolution reaction (OER) is systematically studied in the PrBaCo2O5+δ family. The reduced number of physical/chemical variables combined with in‐depth characterizations such as neutron dif‐fraction, O K‐edge X‐ray absorption spectroscopy (XAS), electron energy loss spectroscopy (EELS), magnetization and scanning transmission electron microscopy (STEM) studies, helps investigating the complex correlation between OER activity and a single perovskite property, such as the oxygen content. Larger amount of oxygen vacancies appears to facilitate the OER, possibly contributing to the mechanism involving the oxidation of lattice oxygen, i.e., the lattice oxygen evolution reaction (LOER). Furthermore, not only the number of vacancies but also their local arrangement in the perovskite lattice influences the OER activity, with a clear drop for the more stable, ordered stoichiometry.