Background: Little data is available in the literature about the role of end tidal oxygen in critically ill patients. We sought to identify the association between the level of respiratory oxygen and clinical outcomes in critically-ill ventilated trauma and burn patients. Methods: A retrospective cohort of 55 trauma and burn patients from 2010 to 2016 was collected. Exposures of interest included a) expiratory end tidal oxygen (ETO2) and b) the difference between FiO2 and ETO2 (uptake). Associations of clinical characteristics with ETO2 and oxygen uptake were examined using a Spearman correlation. The relationships between discharge status, demographics, injury type, severity, and clinical characteristics were examined using chi-square (or Fisher's exact) tests and two-sample t-tests. Multivariable analyses using linear and logistic regression were performed to determine whether expiratory end tidal oxygen or oxygen uptake was an independent predictor of clinical outcomes. Results: Mean age for the patients was 46.3 ± 18.2 years with 41 (74.6%) male and 34 (61.8%) white. In the cohort, 27 (49.1%) of patients had burns and 28 (50.9%) blunt trauma. Oxygen uptake was negatively correlated with lactic acid, minute ventilation, total ICU days, and ventilator days (p < 0.05). Patients who died demonstrated lower oxygen uptake than those alive, oxygen uptake remained significantly associated with discharge status after adjusting for potential confounders (p = 0.028). Conclusion: A narrowed difference between ETO2 and inspiratory oxygen is associated with increased mortality in a cohort of ventilated trauma and burn patients. Future research is needed to further elucidate the role of respiratory oxygen level in larger, prospective studies.