Aim and background: Neutrophil CD64 (nCD64) is evolving as a prognostic biomarker in sepsis. The primary objective of this study was to evaluate whether serial trend of nCD64, procalcitonin (PCT), and C-reactive protein (CRP) predict 28-day mortality in patients with sepsis/septic shock, as per Sepsis-3 criteria. Materials and methods: This prospective, observational single-center cohort study included 60 adult patients (age ≥18 years) with sepsis. Serial biomarker levels with SOFA score were measured at admission (day 0), on day 4, and on day 8. Results: Of the 60 patients, 42 (70%) had septic shock. Biomarker levels at admission did not differ between patients with sepsis and septic shock. Thirty-seven patients survived and 23 were non-survivors by day 28. There was a significant fall in serial trend of all three biomarkers from admission till day 8 (Friedman p < 0.001) in survivors compared to a non-significant change in non-survivors. On multivariate analysis, SOFA score at admission (OR 1.731), more days with vasopressor support (OR 1.077), rise in CD64 from day 0 to day 8 (OR 1.074), and rise in CRP from day 0 to 8 (OR 1.245) were the significant predictors of 28-day mortality (p < 0.05). The highest area under the ROC curve was obtained for more days of vasopressor therapy (0.857), followed by a rise in CD64 from day 0 to day 8 (0.798). Conclusion: Serial trend of biomarkers has prognostic utility. The rise in CD64 from day 0 to day 8 was a good predictor of mortality compared to the trend of other biomarkers.

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