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Sepsis is a life-threatening organ dysfunction with increased incidence of morbidity and mortality. Early diagnosis and prompt therapeutic intervention is the cornerstone of sepsis care. Biomarkers play an important role in sepsis having both diagnostic and prognostic implications. Neutrophil CD64 (nCD64) is a useful candidate biomarker for sepsis. Neutrophil CD64 also known as Fc receptor 1 (FcR1), is a high-affinity receptor present on neutrophils for Fc part of immunoglobulin-G (IgG) heavy chain. Its expression gets strongly upregulated in response to proinflammatory cytokines of infection within 4–6 hours. Neutrophil CD64 integrates function involving both innate and adaptive immune responses. The aim of this review is to present literature about nCD64 as a diagnostic and prognostic marker in patients with sepsis/septic shock. Background The authors searched articles over 13 years, i.e., from 2006 to 2019. They included articles written in English only and further reviewed the reference list of selected articles to obtain potentially relevant articles. Reviews, letters, commentaries, correspondences, case reports, conference abstracts, expert opinions, editorials, and animal experiments were excluded. Articles involving pediatric patients (≤18 years) were also excluded. Review results Several studies have indicated that nCD64 is a highly sensitive and specific marker for the diagnosis of sepsis. Various combinations of biomarkers have been used with nCD64 for a better diagnostic value. Neutrophil CD64 as a prognostic marker in critically ill patients needs to be explored more. Most of the existing literatures have highlighted its prognostic utility based on single value at enrolment. There are limited literatures on prognostic implications of serial trend and kinetics of nCD64. Conclusion Neutrophil CD64 is a useful diagnostic and prognostic marker of sepsis in critically ill patients. Additional studies are needed on nCD64 in sepsis based on sepsis-3 criteria. Further trials with large sample size are needed to establish prognostic implications of serial nCD64 trend. How to cite this article Patnaik R, Azim A, Agarwal V. Neutrophil CD64 a Diagnostic and Prognostic Marker of Sepsis in Adult Critically Ill Patients: A Brief Review. Indian J Crit Care Med 2020;24(12):1242–1250.