Surgery associated with trauma and soft tissue injuries after surgery significantly activates the systemic immune response. If an infection after surgery occurs, the response is even stronger. Due to spontaneous activation of immune response and elevated biomarkers for sepsis and cytokines, posttraumatic complications such as new-coming postoperative infections are difficult to diagnose. Sepsis as systemic inflammatory response syndrome (SIRS) rapidly progresses through severe sepsis to septic shock and organ failure, and with no applied antibiotic treatment, the disease often ends at death of the patients. In the treatment of non-surgery patients, the biomarkers like white cell blood count, C-reactive protein (CRP) or procalcitonin (PCT) proved to be useful in sepsis recognition. However, diagnostics after surgeries are more complicated and these biomarkers are not ideal. The solution is a sepsis biomarker, which would have high sensitivity and specificity, that can improve diagnostic accuracy of sepsis, should also be measured easily by the patients, and should not be too expensive. We think more sensitive and specific biomarkers such as presepsin (sCD14-ST) or CD64 index on neutrophils could be useful. A diagnosis of sepsis should be based on clinical signs, and clinicians should use biomarker that is not only most sensitive and specific but also is cost effective. Furthermore, confirmation of the bacterial or fungal infection with blood cultures or with the use of broad range polymerase chain reaction (PCR), when culturing is impossible, should be performed.