The effects of combined exposure to lead and cadmium on granulose cells were studied. Adult female rats were treated i.p. with either lead acetate (LA) or cadmium acetate (CA) both, alone, or in combination at a dose of 0.05 mg/kg body weight on a daily basis for 15 days. Both metals were accumulated in the ovary after metal exposure. Metal exposure caused a decrease in reduced glutathione content along with elevated lipid peroxidation in all groups. Granulose cells of both cadmium as well as combination group demonstrated a maximum increase in lipid peroxides and catalase activity, along with decreased glutathione status and superoxide dismutase activities. Combined treated animals exhibited an intermediate effect in antioxidant status. However, “in vitro” exposure showed no significant change in antioxidant enzymes in all metal exposed cells. Data from the present study indicates that lead and cadmium in isolation and in combination cause oxidative stress. Lead and cadmium in combination do not show additive or synergistic effect indicating the competition between them due to similarity in electronic affinities. Present study highlights the effects of toxic metals that disturb membrane integrity of cells via ROS and thereby classifying mechanism for altered receptor binding, steroidogenesis, and hormone production.