Perovskite electrocatalysts strongly rely on electronic structure regulation, especially for electron configuration (eg) and conductivity. However, current regulation strategies inevitably involve ambiguous entanglement of crystals, electrons, and spin degrees of freedom. Here, we developed a spin-state regulation method to optimize oxygen evolution reaction (OER) activity by lattice orientation control of LaCoO3 epitaxial films. The different lattice-oriented LaCoO3 films bring different degrees of distortion of the CoO6 octahedron, successfully inducing a spin-state transition of cobalt from a low spin state (LS t2g6eg0) to an intermediate spin state (IS t2g5eg1). X-ray absorption spectroscopy of Co L-edge and O K-edge provides experimental support of spin-state transition in different lattice-oriented LaCoO3 films. As expected, LaCoO3 (100) film possesses optimal eg electron filling, lower adsorption free energy, and higher conductivity, exhibiting better OER performance than the other two films. Our findings demonstrate that electronic state regulation will be a new avenue for the rational design of high-activity perovskite electrocatalysts. Display omitted •A conceptually unique regulation method for perovskite electrocatalysts is described•Synergistic effect contributes to the optimal OER activity•Pure spin-state regulation inspires design of high-activity OER catalysts Electrochemical water splitting plays a key role to meet the growing energy and environmental crises derived from the excessive utilization of fossil fuels. As one of the half reactions, the oxygen evolution reaction (OER) is important in various renewable oxygen-based electrochemical technologies. Perovskites, as prototype efficient OER catalysts, have attracted extensive interest arising from synergic advantages of their structural stability, rich active sites, and wide-range of controllable electronic states. However, the development of perovskite electrocatalysts has been greatly hampered by optimization of eg electrons and electronic conductivity. To enhance the electrocatalytic activity of perovskite, we demonstrated a spin-state regulation method by lattice orientation control of LaCoO3 epitaxial films to obtain superior OER performance. Moreover, this method of electronic state regulation could provide a guide for the rational design of high-activity perovskite electrocatalysts. A unique spin-state regulation method has been proposed to optimize oxygen evolution reaction (OER) activity by lattice-oriented control of LaCoO3 epitaxial films. As expected, LaCoO3 (100) film exhibits a better OER catalytic performance than that of LCO (110) and LCO (111) films, making it superior to most reported perovskite electrocatalysts.