The LOCO2 trial compared a conservative oxygenation strategy with a more liberal approach in patients with moderate-to-severe acute respiratory distress syndrome. The conservative strategy targeted a PaO2 of 55–70 mm Hg, with treatment adjusted to limit oxygen exposure. The trial was stopped early after safety concerns emerged. Conservative oxygenation did not improve 28-day survival, and mortality at 90 days was numerically and statistically worse in the conservative group. Mesenteric ischaemic events also occurred in the conservative-oxygen arm. The study is important because it complicates the narrative that “less oxygen is always better.” Avoiding hyperoxia remains sensible, but pushing arterial oxygen too low may carry its own risks, particularly in patients with severe critical illness. For clinicians, the practical implication is to use oxygen targets thoughtfully and within the context of the whole patient. The appropriate target may depend on disease severity, organ function, chronic hypoxaemia, haemodynamic status and the monitoring strategy being used. LOCO2 fits CritiCARE's repeated focus on oxygen targets, ARDS and ventilator management. It is a useful counterweight to positive findings from smaller oxygen-conservation studies and demonstrates why large pragmatic trials are essential before changing routine ICU targets.