We aimed to investigate the impact of oxytocin on serum thiol/disulphide and malonylyldialdehyde (MDA)/glutathione balance under acute stress (AS) and chronic stress (CS) exposure in rats. Animals were allocated into control (C), AS and CS groups, then the groups subdivided as intranasal oxytocin or saline applied groups, randomly. Animals in the AS or CS groups were exposed to combined cold-immobilisation stress. Salivary corticosterone levels and elevated plus maze (EPM) scores were used to assess stress response. MDA, glutathione, thiol-disulphide levels were measured in the serum samples. Oxytocin treatment attenuated stress response regardless of the stress duration verified by lower corticosterone level and favorable profile in EPM parameters measured. Furthermore, oxytocin modulated oxidant profile suggesting lowered oxidant stress with decreased serum MDA/glutathione and disulfide/native thiol ratios. Oxytocin improves the response of organism to stress via both its anxiolytic and antioxidant effects. That’s why it can be considered as a protective measure to employ methods to increase endogenous oxytocin and/or to apply exogenous oxytocin to prevent stress-induced increase in oxidant stress, which plays a pivotal role in the pathogenesis of various stress-related diseases.