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Sepsis, which kills over 200,000 patients and costs over $20 billion in the United States alone, presents a constant but preventable challenge in the healthcare system. Among the more challenging problems that it presents is misdiagnosis due to conflation with other inflammatory processes, as its mechanisms are identical to those of other inflammatory states. Unfortunately, current biomarker tests can only assess the severity and mortality risk of each case, whereas no single test exists that can predict sepsis prior to the onset of symptoms for the purpose of pre-emptive care and monitoring. We propose that a single test utilizing three, rather than two, biomarkers that appear most quickly in the blood and are the most specific for sepsis rather than trauma, may improve diagnostic accuracy and lead to lessened patient morbidity and mortality. Such a test would vastly improve patient outcomes and quality of life, prevent complications for sepsis survivors, and prevent hospital readmissions, saving the American healthcare system money. This review summarizes the current use of sepsis biomarkers to prognosticate morbidity and mortality, and rejects the current single-biomarker and even combination biomarker tests as non-specific and inaccurate for current patient needs/pro-inflammatory cytokines, general markers of inflammation, and proteins specific to myeloid cells (and therefore to infection) are discussed. Ultimately, the review suggests a three-biomarker test of procalcitonin (PCT), interleukin-6 (IL-6), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to diagnose sepsis before the onset of symptoms.