The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in the stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (SD). During the social defeat procedure, 1 mg/kg of OXT was administered 30 minutes before each episode of SD. Three weeks after the last defeat, the effects of cocaine on conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigm were evaluated. Our results confirm that raising the levels of OXT during social defeat stress can block the long-lasting effects of this type of stress. OXT counteracts the anxiety induced by SD. Moreover, OXT prevents SD-induced increases in the motivational effects of cocaine. Administration of OXT before each social defeat blocked the SD-induced increment in the conditioned rewarding effects of cocaine in the CPP, favors the extinction of cocaine-associated memories in both the CPP and SA, and decreases reinstatement of cocaine-seeking behavior in the SA. In conclusion, the long-lasting effects of SD are counteracted by administering OXT prior to stress.