In lithium-ion (Li-ion) batteries, stresses arise as the results of the mechanical loading and constraint, the Li intercalation induced deformation in the active materials, and the thermal expansion mismatch between the battery components. Such stresses in the separator are of great concern for the safety and durability of the batteries. To assess the stress in the separator, a multiphysics model for a basic Li-ion battery cell including all three types of deformation has been developed. The time and temperature dependent constitutive behavior of a PP separator was characterized and modeled. The multiphysics model was used to analyze the stress in the PP separator. The results showed that the effects of Li intercalation, thermal mismatch and temperature on the stress in the separator are not a simple summation and hence must be considered concurrently. The Li intercalation induced dimensional change in the through-thickness direction can be minimized by design optimization.