ONZIN is abundantly expressed in immune cells of both the myeloid and lymphoid lineage. Expression by lymphoid cells has been reported to further increase after cutaneous exposure of mice to antigens and haptens capable of inducing contact hypersensitivity (CHS), suggesting that ONZIN has a critical role in this response. Here, we report that indeed ONZIN‐deficient mice develop attenuated CHS to a number of different haptens. Dampened CHS responses correlated with a significant reduction in pro‐inflammatory IL‐6 at the challenge site in ONZIN‐deficient animals, compared with wild‐type controls. Together the study of these animals indicates that loss of ONZIN impacts the effector phase of the CHS response through the regulation of pro‐inflammatory factors.