Objective- To evaluate the effects of bupivacaine (B), ketamine (K), and a combination of bupivacaine and ketamine (BK) after lumbosacral epidural analgesia in sheep. Design- Experimental study. Animals- Nine healthy male and non-pregnant female Iranian Chall sheep with mean body weight of 38.9 ± 15.1 kg. Procedures- Animals were selected randomly and three treatments administered. The drugs were administered in the lumbosacral epidural space. The onset and duration of analgesia and sedation were determined and heart rate, respiratory rate, and rectal temperature, were recorded at 0, 5, 10, 15, 20, 30, 40, 50, and 60 min after administration. Analgesia was determined by lack of response to pin pricking and pinch test in the skin of caudal areas. Results- The onset of analgesia was significantly faster in BK than that in B and K alone. Treatments with ketamine, either alone (K) or in combination (BK) lead to mild sedation. The heart rate increased significantly with B treatment at 15 and 20 min, and the respiratory rate showed a significant decrease with K treatment at 10 and 15 min. Conclusion and Clinical Relevance- Epidural administration of bupivacaine/ketamine combination resulted in fast onset and moderate duration of analgesia of caudal areas. The employed doses in BK treatment probably reduced the side effects observed in B and K treatments. It is concluded that the combination of BK could be used epidurally in sheep to perform operations without any marked side effects.