FiO₂ is the fraction of inspired air that is made up of oxygen (O₂). Normal room air is approximately 21% O2, versus 30-100% on a ventilator. High levels of FiO₂ are associated with oxygen toxicity but is generally considered safe over the short term, hence when patients are first put on the ventilator FiO₂ may initially be set to 100% to ensure oxygenation, then down-titrated as appropriate. A goal FiO₂ ≤ 50% is sometimes used; to help reach this goal, PEEP can be increased.

The ability to maintain SpO₂ ≥ 90% with an FiO₂ ≤ 40% is one of the criteria sometimes used to assess readiness for extubation.