Interleukin 22 (IL-22) is a TH17-like cytokine known to specifically activate epithelial cells, thereby strengthening immune defense at host/environment interfaces. Animal studies suggest that IL-22 may play a crucial role in clinical sepsis. However, little is known about IL-22 in sepsis patients. In a single-center university hospital setting, serum IL-22 levels were assessed in 16 patients with the diagnosis of abdominal sepsis, 16 patients who have undergone elective major abdominal surgery without the diagnosis of sepsis, and 21 healthy volunteers. In accordance with current knowledge, we observed enhanced levels of IL-6 and IL-10 in serum specimens of sepsis patients compared with surgical control patients. Here, we report, for the first time, a modest but significant elevation of serum IL-22 detectable in abdominal sepsis patients (P < 0.001). Median serum concentrations of IL-22 were 111.8 pg/mL, 3.4 or 2.0 pg/mL, and 9.3 pg/mL for abdominal sepsis patients, surgical control patients (presurgery or postsurgery), and healthy volunteers, respectively. Interleukin 22 produced in the course of abdominal sepsis may contribute to host defense and stabilization of mucosal barrier functions under conditions of systemic infection.