Since chronic stress has been used widely for studying clinical depression and that brain energy metabolism and oxidative stress might be involved in the pathophysiology of this illness, the objective of this study was investigate the activities of pyruvate kinase, complex II and IV (cytocrome c oxidase) in hippocampus and prefrontal cortex of rats submitted to chronic variable stress. We also evaluated if vitamins E and C administration could prevent such effects. During 40 days adult rats from the stressed group were subjected to one stressor per day, at a different time each day, in order to minimize predictability. The stressed group had gained less weight while its immobilization time in the forced swimming test was greater than that of the control group. Results showed that stressed group presented an inhibition in the activities of complex II and cytochrome c oxidase in prefrontal cortex, while in hippocampus just complex IV was inhibited. Pyruvate kinase activity was not altered in stressed group when compared to control. Vitamins E and C administration prevented the alterations on respiratory chain caused by stress. These data suggest that the impairment of energy metabolism and oxidative stress could be related with the pathogenic pathways in stress related disorders.