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Introduction The aim of the study was to compare the Quick Sequential Organ Failure Assessment tools (qSOFA), and Quick Sequential Organ Failure Assessment-Lactate (LqSOFA) to detect pre-hospital sepsis among patients with or without suspicion of infection. Material and methods Multicenter prospective cohort study in non-traumatic patients attended by Advanced Life Support in the prehospital environment and transferred to the hospital. We collected demographic, physiological, clinical, and analytical variables, main diagnosis, hospital admission and clinical diagnosis of sepsis. Primary outcome was the clinical diagnosis of sepsis in the hospital. Results Between March 1, 2018 and March 31, 2019, we included in our study 1548 participants of whom 82 (5.3%) received a final hospital diagnosis of sepsis. The qSOFA presented an area under the receiver operating characteristic curve (AUROC) to detect sepsis in patients with suspicion and without suspicion of infection of 0.757 (95% CI: 0.65–0.81), compared to LqSOFA with an AUROC to detect sepsis of 0.784 (95% CI: 0.72–0.84). In the group of patients with suspected infection, the LqSOFA for a 2-point cut-off presented an AUROC of 0.773 (95% CI: 0.69–0.85), with an excellent sensitivity of 92.6% (95% CI: 83.9–96.8) and an odds ratio of 8.23 (95% CI: 3.09–21.92). Conclusions An appropriate strategy for reducing the morbidity and mortality from sepsis must necessarily include the prompt identification of this time-dependent pathology by using all the tools at our disposal. The qSOFA and LqSOFA can be used in the prehospital environment and help the diagnosis of suspected sepsis in patients with medical pathology, highlighting the predictive capacity of LqSOFA in the group of patients with suspected infection.