Anesthesia is used in animals to relieve pain during surgical interference or other procedures which were likely causing pain. Safe, effective, and reversible anesthesia requires selecting proper anesthetic agents. This study aimed to evaluate the qualitative and quantitative aspects of total intravenous anesthesia (TIVA) induced by using nefopam/xylazine/ ketamine and propofol combination in local breed donkeys. Nefopam/xylazine/ ketamine and propofol anesthetic combination was evaluated for pain management by using nefopam to provide the maintenance of the anesthetic stage. The onset and duration of anesthetic induction, time of maintenance, and period of recovery were recorded. Furthermore, heart rate, respiratory rate, body temperature, and blood picture were analyzed before and after administration of the combination. Our findings revealed that administration of Nefopam/ xylazine/ ketamine and propofol combination led to a smooth induction with rapid onset within one minute. The anesthetic effect was maintained for approximately 31 minutes after continuous infusion of propofol for standard deviation (19±2 minutes). This was followed by a smooth recovery within approximately 48 minutes after induction of anesthesia. It concluded that nefopam/xylazine/ketamine and propofol infusion is considered satisfactory for pain management and provide satisfactory anesthesia for short surgical procedures in donkeys.