Two total intravenous anesthetic (TIVA) combinations were investigated for their anesthetic efficacy, biochemical effects, and clinical observations in donkeys. The study was carried out on 10 donkeys 5-8 years old and 95 ± 5.9 kg body weight which were equally divided into two groups. Combination (A) composed of Xylazine hydrochloride 1.1 mg/kg, Ketamine hydrochloride 2.2 mg/kg, Diazepam 0.1 mg/kg, and a continuous intravenous infusion of 2 mg/kg propofol. Combination (B) comprised nefopam 0.4 mg/kg, Xylazine 1.1 mg/kg, 2.2 mg/kg Ketamine and continuous intravenous infusion of 2 mg/kg propofol. The onset of anesthesia, duration of induction, maintenance, and recovery periods were recorded. Also, heart, and respiratory rates, body temperature, blood picture, and serum biochemical were assessed before and after administration of each combination. Combination (A) exhibited a rapid onset of induction within 46±  3.8 seconds, maintained anesthesia for 45 minutes after continuous propofol infusion for 19± 2 minutes, followed by very smooth recovery within 68 minutes from induction. In contrast, Combination (B), showed slow induction within 11 minutes, maintained anesthesia for 31 minutes with continuous propofol infusion for 19±2 minutes, and showed smooth recovery within 45 minutes. In conclusion, Combination (A) is considered economically suitable for major surgical interferences. While, Combination (B) is preferred for pain management and shorter surgical interferences.