The quality of sedation and analgesia on behavioral, cardio-pulmonary, and biochemical effects of a novel pre-anesthetic medication, consisting of dexmedetomidine (DEX) alone Vs dexmedetomidine-nalbuphine combination (DEX-NAL) in bucks undergoing total intravenous anesthesia (TIVA) using ketamine and propofol (Ketofol) for induction and maintenance, respectively. Six clinically healthy bucks were randomly assigned into two groups. The first group was subjected to an intravenous injection of DEX (3 μg/kg BW), and the second one was injected with DEX-NAL (DEX 3 μg/kg BW & nalbuphine 0.5 mg/kg BW). Anesthesia was induced by intravenous ketamine (5 mg/kg BW) and maintained through intermittent bolus of propofol (2 mg/kg BW). Sedative, analgesic, behavioral, cardio-pulmonary, and biochemical effects of DEX and DEX-NAL were evaluated before any treatment (s) (baseline), after premedication, after induction and at 5, 15, 30, 45, 60, 75, 90 and 120 minutes after drug administration. The use of DEX-NAL combination provided a deeper, potent, rapid onset, smooth induction and recovery, prolonged sedation, anesthesia, and total recovery time than DEX alone. There were higher scores of behavioral parameters, and significant hemodynamic and cardiovascular stability in DEX-NAL group than DEX group. This study concluded that adding NAL to DEX, a novel pre-anesthetic regimen, before TIVA induced by Ketofol improves the quality of anesthesia and recovery with acceptable cardiopulmonary and biochemical outcomes in goats.