The present study was aimed to compare the efficacy of using three anesthetics protocols of sheep anesthesia by combination of Ketamine (K), Paracetamol (P), Tramadol (T), and Xylazine (X), giving by IV or IM routes. Fifteen healthy adult local breed sheep of both sexes weighing (27.4±2.46) kg and aged (12-14 months) were used and divided into three equal groups. Animals were accommodated in the same environmental conditions. G1 was giving K4 T2 P10 X0.05 by IV route, G2 giving K10 T2 P10 X1 mg/kg by IM route and G3 giving K20 T4 P10 X2.5 mg/kg by IM route. The HR, RR, RT, muscle relaxation, limb, and flank analgesia, and rumen movement were taken before administration of anesthesia and consider as the control reading, then were taken at 5, 10, 15, 20, 30, 45 and 60 minutes or till the end of anesthesia. In G1 the induction time, the surgical anesthesia, and the total recovery time were become 50.6 s, 23 m, and 9.4 m respectively. The HR, RR, and RT were increased, the muscle relaxation, and analgesia were moderate. In G2 the induction time, the surgical anesthesia, and the total recovery time were 5, 36, and 5.6 m, respectively. The HR and RR were decreased, and the RT was increased. The muscle relaxation was deep, analgesia was moderate for 10 minutes. In G3 the induction time, the surgical anesthesia, and the total recovery time were 3.6, 73.4, and 7 m respectively. The HR started stable, then after 15 minutes decreased sharply, The RR was irregular, with apnea, the RT was increased, the muscle relaxation was deep for 35 minutes, and the analgesia was deep for 45 minutes. In conclusion; The (K), (P), (T), and (X) combination as anesthetic protocol is seen suitable for sheep anesthesia. The surgical anesthesia, and the depth of analgesia are increased with the increase of ketamine and xylazine doses, and the addition of tramadol, and paracetamol, enhance the quality of anesthesia and make the induction and recovery are good. The protocol of G2 is seen the best between the three protocols used in this experiment. The protocol of G3 is seen superior in analgesia and duration of surgical anesthesia but with respiratory depression.