Fe and V differ in terms of accessible spin states for all active-site intermediates, which could potentially mean that the most favorable structures are different for Fe and V intermediates (Supporting Information Table ). To understand the effect of ground spin states on geometries and isomer energetics of the key M(IV)=O and M(III)-OH (M = Fe, V) intermediates in hydroxylases, we study active-site isomers for Fe and V intermediates in their corresponding HS (only for Fe), IS, and LS states (Supporting Information Table ). Although Fe(IV)=O and Fe(III)-OH where Fe is d 4 and d , respectively, can access all three spin states, i.e., HS quintet/sextet, IS triplet/quartet, and LS singlet/doublet states, we find that both intermediates strongly prefer an HS ground state consistent with prior experimental and computational studies (Supporting Information Table ). However, V(IV)=O where V is d 1 can only access the LS doublet state, and while V(III)-OH where V is d 2 can access IS triplet and LS singlet states, it strongly prefers an IS ground state (Supporting Information Table ).