SummarySocial stress has long been known to affect physical and psychological health in humans and a variety of animal species. In mice, disruption of the social hierarchy (social disruption, SDR) resulted in significant changes in the phenotype and function of immune cells taken from the spleen. Interestingly, there were considerable individual differences in the development of this splenic response to SDR. Studies have suggested that these individual differences were mediated by behavioral factors such as social hierarchy. To test this hypothesis, social status within cages of male mice was identified before and after SDR. Results showed that in the majority of the cages social order was stable over time. In addition, examination of the association between social status and splenic function showed that the splenic response to SDR in subordinate mice was significantly augmented compared to dominants. This relationship between subordinate social status and the splenic response to social stress was more notable in cages with stable social hierarchies. To sum up, the current study showed a role for socio-behavioral factors in determining the response to stress. This study further demonstrated the complexity of factors playing a role in mediating the physiological response to social stress resulting in considerable individual differences in the response to stress.