OBJECTIVE The aim of this study was to evaluate the combination of bupivacaine and methadone administered epidurally in sheep. METHODS Six healthy female mixed-breed sheep weighing 35-46 kg and aged 12-18 months were included. Each sheep was assigned to receive three treatments: 0.5 mg/kg 0.25% bupivacaine (BP), 0.3 mg/kg 1% methadone (MT) or 0.25 mg/kg bupivacaine and 0.15 mg/kg methadone (BPMT). All drugs were injected into the lumbosacral space through an epidural catheter. Each animal received each treatment at random. Heart rate, arterial blood pressure (systolic, diastolic and mean), respiratory rate, rectal temperature, analgesia, sedation and motor block were determined before treatment and at predetermined intervals. RESULTS The duration of analgesia was 240, 220, and 180 min for BP, MT and BPMT, respectively (P < 0.05). Motor block for all agents was mild to moderate. None or the treatments significantly altered the heart rate, blood pressure or respiratory rate. CONCLUSIONS Our findings suggest that lumbosacral epidural administration of bupivacaine, methadone or a combination of the two drugs can provide perioperative analgesia in sheep as part of their management for surgical procedures in the flank and hindlimbs.