Chloride is an essential cofactor in the oxygen-evolution reaction that takes place in photosystem II (PSII). The oxygen-evolving complex (OEC) is oxidized in a linear four-step photocatalytic cycle in which chloride is required for the OEC to advance beyond the S2 state. Here, using density functional theory, we compare the energetics and spin configuration of two different states of the Mn4CaO5 cluster in the S2 state: state A with Mn1(3+) and B with Mn4(3+) with and without chloride. The calculations suggest that model B with an S = 5/2 ground state occurs in the chloride-depleted PSII, which may explain the presence of the EPR signal at g = 4.1. Moreover, we use multiconformer continuum electrostatics to study the effect of chloride depletion on the redox potential associated with the S1/S2 and S2/S3 transitions.