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Feasibility of ED triage sepsis screening, before diagnostic testing has been performed, has not been established. In a retrospective, outcome-blinded chart review of a one-year cohort of ED adult septic shock patients (“derivation cohort”) and three additional, non-consecutive months of all adult ED visits (“validation cohort”), we evaluated the qSOFA score, the Shock Precautions on Triage (SPoT) vital-signs criterion, and a triage concern-for-infection (tCFI) criterion based on risk factors and symptoms, to screen for sepsis. There were 19,670 ED patients in the validation cohort; 50 developed ED septic shock, of whom 60% presented without triage hypotension, and 56% presented with non-specific symptoms. The tCFI criterion improved specificity without substantial reduction of sensitivity. At triage, sepsis screens (positive qSOFA vital-signs and tCFI, or positive SPoT vital-signs and tCFI) were 28% (95% CI: 16–43%) and 56% (95% CI: 41–70%) sensitive, respectively, p < 0.01. By the conclusion of the ED stay, sensitivities were 80% (95% CI: 66–90%) and 90% (95% CI: 78–97%), p > 0.05, and specificities were 97% (95% CI: 96–97%) and 95% (95% CI: 95–96%), p < 0.001. ED patients who developed septic shock requiring vasopressors often presented normotensive with non-specific complaints, necessitating a low threshold for clinical concern-for-infection at triage.