Recent research focused on the increased level of inflammatory cytokines and decreased the level of anti-inflammatory cytokines in chronically stressed individuals and this physiological state deteriorates further if the individual encounters some pathogens. Few studies have examined the effect of live bacterial infection in a stressed condition and fewer still have examined the effect of exogenous IL-10 and an antibiotic combination as a therapeutic approach to chronic stress and infection. In this study, we evaluated the role of the host’s adrenal-glucocorticoid response to live E. coli infection in the presence of exogenous IL-10 or an antibiotic or both in combination in restraint-stressed mice. Results obtained showed that IL-6, TNF-α and IFN-γ levels were down-regulated, IL-10 level increased significantly (P <0.05), pathogen load from blood was cleared effectively, and these effects were more profound when IL-10 treated stressed animals were administered CIP post-infection compared to the only IL-10 or only CIP treated groups. Moreover, serum C-reactive protein, AChE activity, COX-2 and iNOS expression were also inhibited in these animals. Both IL-10 and CIP treated animals also showed improved exploration and locomotion in OFT and EPM. Thus this study suggests an alternative therapeutic modality where impaired glucocorticoid sensitivity interferes with the appropriate regulation of inflammation. © 2017 National Institute of Science Communication and Information Resources (NISCAIR). All rights reserved.