Typical and atypical antipsychotic drugs have been shown to have different clinical, biochemical, and behavioral profiles. It is well described that impairment of metabolism, especially in the mitochondria, leads to oxidative stress and neuronal death and has been implicated in the pathogenesis of a number of diseases in the brain. Considering that some effects of chronic use of antipsychotic drugs are still not well known and that succinate dehydrogenase (SDH) and cytochrome oxidase (COX) are crucial enzymes of mitochondria, in this work, we evaluated the activities of these enzymes in rat brain after haloperidol, clozapine, olanzapine, or aripiprazole chronic administration. Adult male Wistar rats received daily injections of haloperidol (1.5 mg/kg), clozapine (25 mg/kg), olanzapine (2.5, 5, or 10 mg/kg), or aripiprazole (2, 10 or 20 mg/kg) for 28 days. We verified that COX was not altered by any drug tested. Moreover, our results demonstrated that the atypical antipsychotic olanzapine inhibited SDH in the cerebellum and aripiprazole increased the enzyme in the prefrontal cortex. We also observed that haloperidol inhibited SDH in the striatum and hippocampus, whereas clozapine inhibited the enzyme only in the striatum. These results showed that antipsychotic drugs altered SDH activity but not COX. In this context, haloperidol, olanzapine, and clozapine may impair energy metabolism in some brain areas.