Antidepressants, including selective serotonin reuptake inhibitors, are commonly prescribed for the treatment of affective disorders such as anxiety and depression. The purpose of this study was to investigate the central effects of acute administration of paroxetine (PXT) combined with lipoic acid (LA) on various behavioral models in mice. Paroxetine (10 and 20 mg/kg), LA (100 mg/kg), or vehicle was administered, intraperitoneally, 30 minutes before the tests. The results showed that PXT (10 mg/kg) alone and in combination with LA increased locomotor activity. In the anxiety models studied, an anxiolytic effect was observed after the administration of LA and PXT. In the tail suspension test, PXT at both doses and in combination with LA caused a significant decrease in immobility time. These results indicate possible anxiolytic and antidepressant effects of LA associated with PXT. These data suggest that coadministration of LA and PXT may improve anxiolytic and antidepressant responses, and being more effective than each drug alone. However, further studies are necessary to investigate the mechanism by which antioxidants exert antidepressant or anxiolytic action.