Study hypothesis: Implementation of a new pathway dedicated to septic patients within the emergency department (ED) would improve early management, organ dysfunction, and outcome. Methods: During phase 1, all consecutive adult patients with infection and qualifying quick Sequential Organ Failure Assessment (qSOFA) score upon ED admission were managed according to standards of care. A multifaceted intervention was then performed (implementation phase): educational program, creation of a sepsis alert upon ED admission incorporated in the professional software, together with severity scores and Surviving Sepsis Campaign (SSC) bundle reminders, and dedication of two rooms to the management of septic patients (sepsis unit). During phase 2, patients were managed according to this new organization. Results: Of the 89,040 patients admitted to the ED over the two phases, 2,643 patients (3.2%) had sepsis including 277 with a qualifying qSOFA score on admission (phase 1, 141 patients; phase 2, 136 patients). Recommendations of SSC 3-h bundle significantly improved between the two periods regarding lactate measurement (87% vs. 96%, P = 0.006), initiation of fluid resuscitation (36% vs. 65%, P < 0.001), blood cultures sampling (83% vs. 93%, P = 0.014), and administration of antibiotics (18% vs. 46%, P < 0.001). The Sequential Organ Failure Assessment score between H0 and H12 varied significantly more during phase 2 (1.9 ± 1.9 vs. 0.8 ± 2.6, P < 0.001). Mortality significantly decreased during the second phase, on day 3 (28% vs. 15%, P = 0.008) and on day 28 (40% vs. 28%, P = 0.013). Conclusion: Systematic detection, education, and per protocol organization with a sepsis unit dedicated to the early management of septic patients appear to improve compliance with SSC bundles, organ dysfunction, and short-term mortality. These results warrant to be confirmed by prospective studies.