This study evaluated the antinociceptive effect of dexmedetomidine-nalbuphine vs. dexmedetomidine alone in jacks undergoing field castration under total intravenous anesthesia. Jacks were premedicated with intravenous (IV) dexmedetomidine (5 µg/kg), either alone (Group D, n = 6) or in combination with 0.3 mg/kg nalbuphine (Group DN, n = 6). IV ketamine (1.5 mg/kg) and propofol (0.5 mg/kg) were used to induce general anesthesia, which was maintained by a continuous propofol (0.2 mg/kg/min) IV infusion. The quality of anesthesia, analgesia, and recovery were evaluated. A simple descriptive scale (SDS) was used to measure pain from the recovery time to 6 h later. The DN group exhibited improvements in analgesic and recovery quality and SDS of pain at 1-, 2-, and 3-h post-recovery. There was an apparent improvement in cardiac status, as evidenced by the enhanced heart rate and electrocardiogram findings compared to group D during surgery and recovery time. The DN group had a lower level of inflammatory cytokines, both during the surgery and shortly after recovery. Therefore, the dexmedetomidine-nalbuphine combination prior to IV anesthesia of ketamine and propofol in jacks undergoing field castration resulted in a stable surgical plane of anesthesia, improved antinociception, less pain postoperatively, and better cardiac stability.