Stressful events induce a range of neurochemical and endocrine changes as part of the brain’s adaptive response to such challenges. If the organism is repeatedly stressed, the development or exacerbation of psychopathologies, such as depression and anxiety, can ensue. A potential role for inflammatory factors in these disorders has emerged. In the present experiment, we investigated whether a challenge with interleukin (IL)-6, a pro-inflammatory cytokine commonly associated with depression, elicits anxiety-related behaviours and alters brain expression of inflammatory factors in CD-1 mice, and whether this differed based on the social stressor backdrop on which the cytokine was applied. The combination of an acute social stressor coupled with IL-6 injection enhanced expression of IL-1β, IL-6, and SOCS3 in a time- and brain region- dependent manner. The current results are consistent with the perspective that stress acts on the JAK/STAT pathway to enhance expression of certain pro-inflammatory factors, possibly leading to pathologies.