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We evaluated the ratio of delta neutrophil index (DNI) to albumin (A) in patients receiving early goal-directed therapy (EGDT) to determine the prognostic significance of the DNI/A ratio as a marker of early mortality in critically ill patients with suspected sepsis.We retrospectively analyzed records from a prospective EGDT registry in an emergency department (ED) and screened eligible adult patients who were admitted to the ED with severe sepsis and/or septic shock. The new DNI/A ratio was calculated as the DNI value on each hospital day divided by the initial albumin level on ED admission. The clinical outcome was mortality after 28 days.A total of 120 patients receiving EGDT were included in this study. Multivariate Cox proportional-hazard models revealed that higher DNI/A ratios on day 1 (hazard ratio [HR], 1.068; 95% confidence interval [CI], 1.01–1.13; P = .0209) and the peak day (HR, 1.057; 95% CI, 1.001–1.116; P = .0456) were independent risk factors for mortality at 28 days. Our study demonstrated that the increased trend toward 28-day mortality was associated with a DNI/A ratio greater than 8.4 on day 1 (HR, 2.513; 95% CI, 0.950–6.64; P = .0528) and a higher DNI/A ratio (> 6.4) on the peak day (average, 4.2 days; HR, 2.953; 95% CI, 1.033–8.441; P < .001) in patients with severe sepsis receiving EGDT.The ratio of DNI to serum albumin on ED admission is a promising prognostic marker of 28-day mortality in patients with severe sepsis receiving EGDT.