Historically, free-ranging musk oxen (Ovibos moschatus) were anesthetized with potent opioids such as etorphine, which are often associated with marked respiratory depression. The goal of this study was to investigate alternatives to the etorphine–xylazine combination (EtXy) traditionally used in this species. First, the potential benefit of postinduction butorphanol administrations to musk oxen anesthetized with EtXy was assessed. Then, the use of butorphanol–azaperone–medetomidine (BAM-II) as an alternative to the use of potent opioids for the immobilization of free-ranging musk oxen was evaluated. Eighty-nine musk oxen were ground darted with either a combination of EtXy (n = 52) or BAM-II (n = 37), and 10 animals from the EtXy group received an IM injection of butorphanol at 1 mg/mg of etorphine (EtXyB). Intranasal oxygen (1 L/100 kg per minute) was administered to all animals. Respiratory rate, heart rate, peripheral capillary oxygen saturation (SpO₂), end-tidal carbon dioxide (EtCO₂), and rectal temperature were compared between groups. Postinduction butorphanol injection was associated with a decrease in heart rate (P = 0.001) and increases in respiratory rate (P < 0.001), rectal temperature (P < 0.001) and SpO₂ (P < 0.001), but did not affect EtCO₂ (P = 0.069). Musk oxen anesthetized with BAM-II had a significantly lower EtCO₂ (P = 0.009) and heart rate (P = 0.009) compared with musk oxen anesthetized with EtXy or EtXyB, and a higher SpO₂ compared with animals anesthetized with EtXy (P < 0.001). There was no significant difference between induction (P = 0.98) or recovery (P = 0.74) time for the three protocols used. This study provides evidence that postinduction butorphanol administration added to the etorphine–xylazine protocol can decrease respiratory depression. Additionally, BAM-II can be used as an affective drug combination to immobilize musk oxen in their natural environment.