Surgical intervention is an inseparable part of the management of serious surgical disease. However, surgery also presents a potential risk related to the so-called surgical injury causing immune response. When dysregulated the immune activation is able to cause local complications (i.e. wound dehiscence, impaired healing). Systemic decompartmentization of the immunologic disturbance can negatively influence long-term outcomes (i.e. hospital length of stay, mortality). Due to aseptic conditions in the operating room, such an immune activation is almost always of sterile nature. This involves the release of alarmins, protein-based molecules of the damage-associated molecular patterns family. The group includes e.g. high-mobility group box 1, heat-shock proteins, proteins S100A, and more. Under normal conditions, alarmins fulfil their physiologic intracellular functions. When the cell is stressed and/or damaged, alarmins are released into the extracellular space where they probably play their cytokine-like roles activating preferably the innate immune system. A number of experimental and clinical publications have been published concerning the role of alarmins in various acute and chronic diseases. However, to date a potential relationship between alarmins and surgical injury has not been extensively studied. Identification of alarmins that influence the pathological physiology of surgical trauma might play a role in the improvement of monitoring and predicting outcomes after major surgery.Key words: alarmins immune response major surgery sterile injury.