In situ experiments combining X-ray absorption spectroscopy (XAS) and electrochemistry have now become an indispensable tool for understanding the mechanisms of operation, structure, and the modes of degradation of electrocatalysts under operational conditions. Herein, the design of a gas- and liquid-tight spectroelectrochemical cell (SEC) and an experimental protocol for the simultaneous collection of high-quality XAS and electrochemical data are introduced. The effects of the working electrode, loading of active material, and X-ray damage are demonstrated and interpreted by an example of a well-known heterogenite-like cobalt oxide water oxidation catalyst. The SEC permitted reproducible X-ray absorption near edge structure to be collected with a resolution of at least 0.05 eV (equivalent to approximately 0.02 unit oxidation state sensitivity) and allowed X-ray-mediated photoeffects to be examined in detail. Furthermore, tracking of the potential-dependent changes in the oxidation state of a cobalt oxide catalyst with high precision and reproducibility is demonstrated. These in situ XAS data are correlated with a previous detailed electrokinetic analysis to identify the nature of the active state of the heterogenite-like water oxidation catalyst and conclude that metal oxidation states higher than IV are not involved in the catalytic mechanism. Finally, the implications of the significantly different timescales of the probed electron transfer events and the XAS analysis on the interpretation of the in situ spectroelectrochemical data are critically discussed, focusing on the mechanism of the water oxidation reaction.