AbstractBackgroundOxygen therapy is a common treatment in the intensive care unit (ICU) with both potentially desirable and undesirable long‐term effects. This systematic review aimed to assess the long‐term outcomes of lower versus higher oxygenation strategies in adult ICU survivors.MethodsWe included randomised clinical trials (RCTs) comparing lower versus higher oxygen supplementation or oxygenation strategies in adults admitted to the ICU. We searched major electronic databases and trial registers. We included all non‐mortality long‐term outcomes. Prespecified co‐primary outcomes were the long‐term cognitive function measures, the overall score of any valid health‐related quality of life (HRQoL) evaluation, standardised 6‐min walk test, and lung diffusion capacity. The protocol was published and prospectively registered in the PROSPERO database (CRD42021223630).ResultsThe review included 17 RCTs comprising 6592 patients, and six trials with 825 randomised patients reported one or more outcomes of interest. We observed no difference in cognitive evaluation via Telephone Interview for Cognitive Status (one trial, 409 patients) (mean score: 30.6 ± 4.5 in the lower oxygenation group vs. 30.4 ± 4.3 in the higher oxygenation group). The trial was judged at overall high risk of bias and the certainty of evidence was very low. Any difference was neither observed in HRQoL measured via EuroQol 5 dimensions 5 level questionnaire and EQ Visual Analogue Score (one trial, 499 patients) (mean score: 70.1 ± 22 in the lower oxygenation group vs. 67.6 ± 22.4 in the higher oxygenation group). The trial was judged as having high risk of bias, the certainty of evidence was very low. No trial reported neither the standardised 6‐min walk test nor lung diffusion test.ConclusionThe evidence is very uncertain about the effect of a lower versus a higher oxygenation strategy on both the cognitive function and HRQoL. A lower versus a higher oxygenation strategy may have a little to no effect on both outcomes but the certainty of evidence is very low. No evidence was found for the effects on the standardised 6‐min walking test and diffusion capacity test.