Sepsis represents a dysregulated immune response to infection that leads to organ dysfunction. Host response biomarkers play a critical role in diagnosis, early recognition of organ dysfunction, risk stratification, prognostication, and patient management, including antibiotic stewardship. Biomarkers may also be helpful for trial enrichment to identify suitable patients and/or risk categorization for an intervention. A wide range of biomarkers, measured by a host of different technologies, are being investigated to discriminate a systemic inflammatory response syndrome (SIRS) rapidly, which is an excessive defensive body's response to a harmful stressor (for example, infection, trauma, surgery, acute inflammation, ischemia or reperfusion, or cancer) or early identification of infection-triggered organ dysfunction (sepsis). The humoral innate immune response consists of multiple components, including fluid phase pattern recognition molecules (PRMs) and the complement system. PRMs include C-reactive protein (CRP), serum amyloid P component (SAP), and pentraxin 3 (PTX-3). The rise in CRP level is primarily induced by interleukin (IL)-6 and IL-1β acting on the gene responsible for CRP transcription during the acute phase of an inflammatory process. CRP is a pentameric acute-phase reactant protein whose conformation facilitates the ability to trigger complement activation and activate platelets, monocytes, and endothelial cells. Several potential biomarkers for monitoring sepsis have been investigated, including white blood cell count (WBC), C-reactive protein, (CRP), lactate, and procalcitonin (PCT). During the last decade Heparin binding protein (HBP) has attracted interest as a biomarker for severe bacterial infection including sepsis and meningitis. HBP also known as Cationic Antimicrobial Protein of 37 kDa (CAP37) was identified in 1984 and is produced by neutrophils, stored in intracellular vesicles, and rapidly released upon stimulation by pathogen associated microbial patterns, PAMPs. Elevated HBP levels have been shown to correlate with hypotension and organ dysfunction in patients with bacterial sepsis but failed to distinguish patients with septic shock from other causes of shock Hepcidin plays a role in innate immunity through its interactions with IL-6 and other pro-inflammatory cytokines. The ability to sequester iron within cells to prevent its availability for pathogenic or neoplastic growth appears to be largely dependent on hepcidin stimulation by IL-6. This innate defense may help protect against many pathogens, including streptococcal and malarial species. The severity of sepsis depends on several host factors, such as age, comorbidities, and immune status, as well as pathogen factors such as virulence, microbial species, and infectious load. In spite of the sepsis-3 criteria presented as a consensus document 2016 the diagnosis is often a challenge in critically ill patients