BackgroundIn septic patients, hyperoxia may help with its bactericidal effects, but it may cause systemic impairments. The role of hyperoxia and the appropriate oxygen target in these patients is unknown. The aim of this systematic review was to summarize the available literature.MethodsWe conducted a systematic search screening PubMed and Cochrane Library. Studies on adult patients with sepsis or septic shock and admitted to ICU addressing the topic of hyperoxia were included and described.ResultsWe included 12 studies, for a total of 15.782 included patients. Five studies were randomized controlled trials (RCTs) or analyses from RCTs, three were prospective observational studies, and four were retrospective observational studies. The definition of hyperoxia was heterogeneous across the included studies. Mortality was the most frequent outcome: six studies showed an increased rate or risk of mortality with hyperoxia, three found no differences, and one a protective effect of hyperoxia. At the critical appraisal assessment stage, no major methodological flaws were detected, except for a single-center, pilot study, with a lack of adjustment for confounders and imbalance between the groups.ConclusionThe optimum range of oxygen level able to minimize risks and provide benefits in patients with sepsis or septic shock seems still unknown. Clinical equipoise between hyperoxia and normoxia is uncertain as conflicting evidence exists. Further studies should aim at identifying the best range of oxygenation and its optimal duration, investigating how effects of different levels of oxygen may vary according to identified pathogens, source of infection, and prescribed antibiotics in critically ill patients with sepsis and septic shock.Supplementary InformationThe online version contains supplementary material available at 10.1186/s44158-023-00096-5.