In this study, the stress generation of LiCoO2 with realistic 3D microstructures has been studied systematically. Phase field method was employed to generate the 3D microstructures with different grain sizes. The effects of grain size, grain crystallographic orientation, and grain boundary diffusivity on chemical diffusion coefficient and stress generation were studied using finite element method. The calculated chemical diffusion coefficient is about in the range of 8.5 × 10−10 cm2/s–3.6 × 10−9 cm2/s. Stresses increase with the increase of grain size, due to more accumulation of Li ion near the grain boundary regions in larger grain size systems, which causes a larger concentration gradient. Failure is more likely to occur in large grain systems. The chemical diffusion coefficients increase with increasing grain orientation angle irrespective of grain boundary diffusivity, due to alignment of global Li ion diffusion path with high grain orientations. Grain boundary diffusivity has opposite effect on the hydrostatic stress. As small grain boundary diffusivity, the stress increases with increasing grain orientation angle, due to grain boundary blockage of Li ion diffusion. In contrast, with large grain boundary diffusivity, the stress decreases with increasing grain orientation angle due to reduced concentration gradients in grain boundary regions.