A new paradigm for the high- and low-spin forms of the S state of nature's water-oxidizing complex in Photosystem II is found. Broken symmetry density functional theory calculations combined with Heisenberg-Dirac-van Vleck spin ladder calculations show that an open cubane form of the water-oxidizing complex changes from a low-spin, = 1/2, to a high-spin, = 5/2, form on protonation of the bridging O4 oxo. We show that such models are fully compatible with structural determinations of the S state by X-ray free-electron laser crystallography and extended X-ray absorption fine structure and provide a clear rationale for the effect of various treatments on the relative populations of each form observed experimentally in electron paramagnetic resonance studies.