Background: Serious trauma due to various factors is a major global public issue, and sepsis is a major cause of trauma-associated mortality. Timely diagnosis and suitable treatment of post-traumatic sepsis are crucial to improve the hospital outcome of traumatic patients. IL-28 is a newly discovered member of IFN-lambda family with multiple functions in inflammatory response. To date, its role in the pathogenic mechanisms of post-traumatic sepsis still remains unknown.Methods: In total, 20 healthy controls, 55 traumatic patients without sepsis and 54 traumatic patients with sepsis were enrolled in this study. Serum IL-28A/B levels were investigated by ELISA.Results: IL-28A/B levels were significantly increased in traumatic patients compared to healthy volunteers. Moreover, septic trauma patients displayed a significant increase in IL-28A/B levels compared with non-septic patients. In septic patients, IL-28A/B were negatively correlated with IFN-gamma, IL-5, IL-13 and IL-17, and posi-tively associated with IL-10. Moreover, IL-28A (AUC: 0.821, 95 %CI: 0.693-0.949) and IL-28B (AUC: 0.811, 95 % CI: 0.691-0.931) were both beneficial to predict increased mortality risk in septic trauma patients, though there was no statistical difference in the predictive value between them.Conclusions: Early serum levels of IL-28A/B were associated with the development of post-trauma sepsis and could be applied to assess the outcome of traumatic patients with sepsis. Thus, IL-28 may be a potential indicator for post-traumatic sepsis.