A separator is a membrane that prevents the physical contact between the positive and negative electrodes while enabling ionic transport. The integrity of the separator is vital to the performance and reliability of a battery. This paper presents finite element stress analysis for the separator in a lithium-ion battery using a macro-scale battery cell model. In this model, the porous electrodes were treated as homogenized media and represented with the effective properties estimated using the rule of mixtures. To compute the deformation due to lithium (Li) intercalation & deintercalation and temperature variation, the Li concentration distribution and temperature change due to electrochemical reactions must be known. These parameters were computed using a multi-physics model in COMSOL and mapped to the macro-scale model in ANSYS. Numerical simulations were conducted to identify the locations and magnitudes of the maximum strain and stress of the separator in the pouch cell. The effects of temperature change and the effective friction between separator and its surrounding electrodes were also investigated.