To evaluate the sedation quality of an IM injection of a commercially available medetomidine-vatinoxan combination (ZEN) in healthy goats and sheep and discern species differences in cardiopulmonary parameters. 10 apparently healthy adult university-owned research Black Bengal-crossbreed goats and 10 adult Gulf Coast native and Katahdin sheep were enrolled in this prospective experimental study from June 27 to July 27, 2023. All animals were sedated on 1 occasion with 0.06 mL of ZEN/kg, IM (0.03 mg of medetomidine/kg and 0.6 mg of vatinoxan hydrochloride/kg). Cardiopulmonary variables including heart rate, arterial blood pressure, and arterial blood gas parameters were recorded along with sedation depth and duration. Any animals still sedated after 150 minutes received 0.01 mg of atipamezole/kg. The mean ± SD of the total sedation time for sheep and goats was 102.80 ± 10.90 minutes and 133.50 ± 32.63 minutes, respectively. Profound reliable sedation was achieved in all but 1 animal. Hypoxemia was observed in sheep and goats (11 of 20 animals total). Hypotension was seen in 3 of 10 goats. In sheep and goats, ZEN at 0.06 mL/kg, IM, caused profound sedation. Total sedation time was significantly longer in goats than in sheep. In the presence of oxygen supplementation, ZEN at 0.06 mL/kg, IM, may be an acceptable sedation choice for apparently healthy Gulf Coast native and Katahdin sheep, but not goats; however, preexisting hypokalemia or pulmonary disease are contraindications for the use of ZEN in sheep.