Social defeat involves a clear physical component in the form of fight-induced injuries. The impact of body injuries on the immune response is not yet well known. In this study we compared the endocrine and immune responses to two types of social defeat in mice, one limiting the occurrence of skin injuries (mild social stress, MSS), and the other not (social disruption stress, SDR). In the two situations, six defeats were applied within 1 week. Plasma corticosterone and IL-6 levels were measured in blood samples taken after social defeat. Reactivity to LPS and sensitivity to corticosterone (CS) of spleen cells was assessed by measuring the in vitro production of cytokines (IL-6, IFN-gamma and IL-10) in response to LPS under a range of increasing concentrations of CS. The two types of stressors induced a similar plasma corticosterone response, but SDR mice showed significantly higher plasma IL-6 than MSS mice. Splenocytes from SDR but not from MSS mice produced more IL-6 and IL-10 in response to LPS and presented an altered responsiveness to CS in comparison to control mice. We conclude that the procedure involving fights and skin injuries was able to modulate the immune response in the spleen, whereas the procedure preventing the occurrence of fights did not. The increased immune reactivity observed in the fight-associated procedure could result from either a stronger psychological stress or a direct immune activation through the wounds.