Background: Aneurysmal subarachnoid hemorrhage (SAH) is an acute cerebrovascular disease associated with high mortality and long-term functional impairment among survivors. Systemic infammatory responses after acute injury and nosocomial infections are frequent complications, making the management of these patients challenging. Here, we hypothesized that sepsis might be associated with early and long-term mortality and functional outcomes. Our objective was to defne the incidence of sepsis, diagnosed prospectively with the Sepsis-3 criteria, and to determine its impact on mortality and functional outcomes of patients with SAH. Methods: We prospectively included all adult patients with aneurysmal SAH admitted to the intensive care unit (ICU) of a reference center between April 2016 and May 2018. Daily clinical and laboratory follow-up data were analyzed during the frst 14 days, with data collected on sepsis according to the Sepsis-3 criteria. The main outcome was the functional outcome using the Modifed Rankin Scale (mRS), which was assessed at hospital discharge and 3, 6 and 12 months post-discharge. Results: In total, 149 patients were enrolled. The incidence of sepsis was 28%. Multivariable logistic regression analysis revealed that death or functional dependence (defned as an mRS score of 4 to 6) at hospital discharge was independently associated with sepsis (OR 3.4, 95% CI 1.16–9.96, p=0.026) even after controlling for World Federation of Neurological Surgeons (WFNS) Scale (OR 4.66, 95% CI 1.69–12.88, p=0.003), hydrocephalus (OR 4.55, 95% CI 1.61–12.85, p=0.004) and DCI (OR 3.86, 95% CI 1.39–10.74, p=0.01). Long-term follow-up mortality rates were signifcantly diferent in the septic and nonseptic groups (log-rank test p<0.0001). The mortality rate of septic patients was 52.5%, and that of nonseptic patients was 16%. Conclusion: Sepsis plays a signifcant role in the outcomes of patients with SAH, afecting both mortality and longterm functional outcomes. Combining high-level neurocritical care management of neurological complications and the optimal diagnosis and management of sepsis may efectively reduce secondary brain injury and improve patients’ outcomes after SAH.