The gender difference in normal immune function has been well documented, however, there is only limited information regarding whether such a difference occurs after injury. To investigate this, we examined cell-mediated immune responses in male and female mice given a 15% total body surface area dorsal scald or sham injury. Both delayed-type hypersensitivity (DTH) and splenocyte proliferative responses were significantly suppressed in males at 1 day and in females at 7 and 10 days post burn (P < 0.01). The decreased splenocyte proliferation was found to be macrophage-dependent and suppression of both immune parameters corresponded with elevated interleukin-6 (IL-6) levels. Furthermore, post-burn treatment with an anti-IL-6 antibody partially restored the DTH response in males at 1 day and females at 10 days post injury and completely restored splenocyte proliferation. These data demonstrate a possible mechanism for the gender difference in cell-mediated immune responses after thermal injury.