Background <p>The randomized controlled trial, TRAUMOX2, compared early restrictive vs. liberal oxygen strategies for trauma patients. The objective of this substudy was to quantify the occurrence and duration of hypoxemic episodes during the trial’s eight-hour intervention.</p> Methods <p>This observational substudy analyzed a subset of patients at two trial sites in Denmark. Continuous pulse oximetry recorded arterial oxygen saturation (SpO₂) during the intervention. The primary outcome was the proportion of patients who had episodes of hypoxemia with SpO₂ &lt; 90% for at least five minutes. Additionally, the study assessed differences in the occurrence and duration of hypoxemia between the restrictive and liberal oxygen groups.</p> Results <p>This substudy included 82 patients. After secondary exclusion, 60 patients (median age, 49 years [interquartile range 33–61] and 75% male) were analyzed. Three out of 60 patients (5%) had at least one episode of SpO₂ &lt; 90% for at least five minutes (95% confidence interval 1–14%); Two patients in the restrictive oxygen group and one in the liberal oxygen group. Two episodes occurred during initial resuscitation, and one episode occurred in the intensive care unit following a procedure related to thoracic injuries. </p> Conclusions <p>In this substudy of 60 patients from the TRAUMOX2 trial, hypoxemia (SpO₂ &lt; 90% for at least five minutes) was observed in 5% of patients, with no difference between the restrictive and liberal oxygen groups. These findings suggest that, among trauma patients not already requiring continuous monitoring, such episodes of hypoxemia are relatively rare early post-trauma.</p>