Abstract Background Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO₂ > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO₂ ≥ 0.60 during hyperoxemia). Results Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO₂ < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO₂ use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO₂ use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO₂. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO₂ use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO₂ use, compared to 39% in a propensity-matched sample of normoxemic (PaO₂ 55–100 mmHg) patients (P = 0.47). Conclusions Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073