Sepsis is complicated in several pathophysiological manners regarding the perfusion, intestinal epithelial integrity, enzymatic response, coagulation, and mucosal immune system (MIS) [1], [2]. Sepsis remains a main cause of mortality in ICU patients, and so is a main concern for human health globally. In sepsis, bacteria and pathogen-associated-molecular patterns (PAMPs), including PG, LPS, and bacterial DNA, can be recognized by toll-like receptors (TLR2 and TLR4) upon the surface of neutrophils, macrophages, DCs, and even IECs [3]. Thus, DCs and intestinal macrophages as part of the MIS can detect luminal PAMPs via trans-epithelial dendrites (TEDs) [1], [2]. In addition, sepsis-invading bacteria directly or indirectly activate several inflammatory pathways that contribute to sepsis. The main mechanism involved in these signaling pathways is the hyperactivation of neutrophils, monocytes and macrophages and subsequent release of cytokines [4], [5]. Critically ill patients usually undergo substantial pathophysiological changes that affect the function of several organs. Primary initiation of effective antibiotic therapy is critical to saving the lives of critically ill patients with sepsis. In this regard, rapid and specific diagnosis of invading bacteria is essential so that appropriate antibiotics and therapies can be prescribed [5], [6]. Early accurate profiling of pathogenic bacteria in patients with sepsis is crucial to optimize antibiotic therapy and patient survival. Findings in recent years indicated, the biosensor was successfully applied to in detection of sepsis complicate bacteria and showing good consistence and practicability [6], [7]. The developed biosensors provide a sensitive, rapid, reliable and culture-independent approach to efficiently determine multiple pathogenic bacteria for the sepsis management. In recent years, various biosensors have been developed to sepsis management using different biomarkers [6], [7]. In this review, considering the variety and breadth of developed biosensors, while reviewing the recent advances in sepsis biosensors, we have had a brief introduction to sepsis and subsequent conventional and routine methods in sepsis management.