One of the most promising approaches to produce sustainable energy is hydrogen evolution by water splitting. Since water electrolysis is limited by the high overpotential required for the water oxidation reaction, electrocatalysts are applied to reduce the activation energy necessary for this reaction. However, primary catalysts may chemically convert to other compounds during the reaction. Therefore, the physicochemical and electrochemical changes of catalysts used over a long time need to be investigated in detail to understand the real operating catalyst. In this work, we have observed long-term microstructural changes and amorphization of La0.65Sr0.35MnO3 when used as a catalyst in water -electrolysis at near neutral pH. Microscopic and electrochemical analyses show that the catalyst changed at the molecular level. This study revealed that an entirely different catalyst evolved from the original material over the course of the water oxidation reaction. This observation revealed the importance of the study of the long-term stability and reactivity of La0.65Sr0.35MnO3 toward the water oxidation reaction. Published by Elsevier Ltd on behalf of Hydrogen Energy Publications LLC.