Etorphine based immobilization protocols are reported to be effective in pronghorn; however, information on cardiorespiratory effects is limited. The objective of this study was to evaluate the efficacy and cardiopulmonary effects of etorphine, medetomidine, midazolam, and azaperone for immobilization in captive pronghorn. Additionally, the effects of endotracheal intubation and manual ventilation on cardiopulmonary variables were assessed. A combination of 5 mg etorphine, 10 mg medetomidine, 2.5 mg midazolam, and 5 mg azaperone was administered by hand or via dart to 10 pronghorn. Five pronghorn were endotracheally intubated once recumbent and manually ventilated. Oxygen at a flow of 6 L/min was supplemented to all animals. Induction and recovery times were recorded, and during recumbency vital parameters and arterial blood samples were collected. Time to lateral recumbency was 3.8 ± 1.25 min. Marked hypoxemia and hypercapnia was observed in both spontaneously breathing and manually ventilated pronghorn. Hypercapnia improved significantly in manually ventilated pronghorn compared to spontaneously breathing animals. All pronghorn recovered rapidly after reversal with 150 mg naltrexone and 30 mg atipamezole. Administration of etorphine, medetomidine, midazolam, and azaperone resulted in excellent chemical immobilization in pronghorn. Significant hypoxemia and hypercapnia occurred and oxygen supplementation, endotracheal intubation, and manual ventilation is recommended.