We report that a model complex of the Photosystem II-Water Oxidizing Complex (PSII-WOC) facilitates, exclusively, photocatalytic water oxidation from non-potable water sources like seawater, under suitable conditions. When the manganese cubane cluster [Mn4O4L6]+, (L = (p-MeO-Ph)2PO2), 1+, is incorporated within a Nafion membrane deposited on an electrolytic anode that is poised at 1.00 V (vs. Ag/AgCl) and illuminated with light, catalysis of only water oxidation is observed in aqueous solutions of sodium chloride, including seawater. No chlorine formation can be detected. This effect is comparable to the ability of the PSII-WOC in marine and hypersaline organisms to catalyze, exclusively, water oxidation with chloride present within the WOC as an essential cofactor for activity. It stands in clear contrast to commercial water electrolyzers which generate chlorine gas at their anodes when filled with seawater. Investigations suggest that this effect originates largely in electrostatic repulsion of anionic chloride ions by the Nafion support. In this respect it also appears similar to the PSII-WOC, which harnesses a proteinaceous, proton-conducting environment with high cation affinity in its active site. Solar seawater electrolysis of this type offers a potentially unlimited source of clean hydrogen fuel for a future, pollution-free economy. © 2011 Elsevier B.V. All rights reserved.