Background and aim: Sepsis is a systemic inflammatory response to infection after the invasion of host microbial pathogens into the bloodstream that is followed by multiple organ dysfunction and immune suppression leading to susceptibility to nosocomial infections. Sepsis pathogenesis is complex and its mechanism is not yet fully clarified. In addition, the complexity of clinical protests, the development of antibiotic resistance and, ultimately, chronicity of the disease has led researchers to find new directions in this context. So, the search for sepsis biomarkers may be useful to identify patients, evaluate the response to treatment, differentiation of sepsis from local and even assist clinicians in differentiating patients with sepsis from non-infectious SIRS patients. Search method: This study is a systematic review and data are collected from PubMed, Scopus, Science Direct and EMBASE databases. Information are acquired by using 5 keywords (as: Biomarker, Diagnosis, Infectious Diseases, Sepsis, Treatment) from ultimately 40 articles of 1999 to 2015. Findings and results: Although CRP is used as the most common biomarkers in the identification of sepsis, but other markers like Proinflammatory cytokines and chemokines, proteins such as Procalcitonin, monocytes and lymphocytes surface markers, markers of immune paralysis phase as anti-inflammatory cytokines, HBP, PSP, can identify severe sepsis before organ dysfunction and reduce the mortality rate associated with severe sepsis. Conclusion: Sepsis as the most important cause of death among critically ill patients in developed countries and is one of the main causes of mortality in hospitalized patients despite the availability of potentiated antibiotics and advanced medical treatments. This enables researchers to use biological markers clinically as diagnostic and preventive tools at intensive care to improve outcomes of their infection.