This study compared the physiologic effects of carfentanil–xylazine anesthesia in elk administered nasal oxygen or medical air. Eight female 5 ± 2-yr-old (mean ± SD) captive elk (Cervus canadensis manitobensis) weighing 245 ± 20 kg and habituated to chute restraint were studied in a randomized crossover. Nasal insufflation of oxygen or medical air (10 L/min) was provided prior to and throughout anesthesia. Baseline data were collected before i.m. injection of carfentanil (10 μg/kg) and xylazine (0.2 mg/kg). Arterial blood gases (PaO₂ and PaCO₂), arterial blood pressure, heart and respiratory rate, and observations of muscle rigidity and movement were collected every 3 min for 30 min. Drugs were antagonized at 30 min with i.m. naltrexone (1 mg/kg) and tolazoline (2 mg/kg). Induction and recovery were significantly faster (mean ± SD) in elk receiving oxygen (208 ± 39 and 333 ± 63 sec, respectively), vs. medical air (306 ± 84 and 532 ± 201 sec). Elk receiving oxygen had a significantly higher PaO₂ and PaCO₂, and significantly lower pH and heart rate. Minimum PaO₂ was 75 ± 30 mm Hg (oxygen), and 28 ± 6 mm Hg (air). Maximum PaCO₂ was 89 ± 5 mm Hg (oxygen), and 64 ± 4 mm Hg (air). Frequency of rigidity and movement decreased when PaO₂ ≥ 70 mm Hg. Animals breathing air demonstrated slower inductions and recoveries, severe hypoxemia, and increased rigidity and movement. Oxygen administration reduced hypoxemia and improved anesthesia quality, but caused prolonged periods of apnea, and moderate to severe hypercarbia and respiratory acidosis.