An 8-year-old Pêga breed donkey that presented with a history of persistent enlargement of the right leg was diagnosed with a rhabdomyosarcoma by surgical exploration and biopsy. The tumoral mass involved the medial and posterior aspects of the thigh. At presentation, the donkey was extremely painful and reluctant to walk. Initial physical examination showed a heart rate of 60 beats/min, respiratory rate of 32 breaths/min, and a rectal temperature of 100.2°F. Venous blood was collected for a CBC and biochemistry. Postoperative care included antibiotic (potassium penicillin and gentamicin) and anti-inflammatory (phenylbutazone and dexamethasone). The donkey was very painful in the immediate postoperative period and developed dehiscence of the incision. It was unable to bear weight on the affected limb, very reluctant to walk, and lying down in sternal recumbency most of the time. Heart and respiratory rates ranged from 60 to 90 and 20 to 32, respectively. Because of the poor prognosis, euthanasia was indicated but the owner decided to keep the donkey alive to try semen collection. In order to improve life quality and making the semen collection possible, the anti-inflammatory therapy was stopped and an analgesic therapy with epidural opioids was selected. A 20-gauge epidural catheter was inserted in the first intercoccygeal space through an epidural Huber point needle. With the purpose of reaching the lumbosacral area, 20 cm of the catheter was advanced cranially from the needle tip. During 3 days, a combination of morphine (0.1 mg/kg) and tramadol (0.5 mg/kg) was administered daily with a total volume of 20 ml. During the first 24 hours after the first administration, heart rate ranged from 62 to 64 and respiratory rate from 20 to 24. It was not observed to have any adverse effect. The donkey improved during treatment standing most of the time and eating better. It was easier to hand walk, although it was not completely able to bear weight in the affected limb. Even during treatment, the donkey reacted intensely when the surgical area in the caudal aspect of the thigh was manipulated. On the forth day, it tried to copulate and semen was successfully collected by manipulation of the penis. As the semen was not classified as good enough to be frozen, the donkey was euthanatized. On post-mortem examination, the position of the catheter in the epidural canal was observed and 20 ml of methylene blue solution injected through the catheter before euthanasia. It was enough to totally stain the segment of epidural canal from the first intercoccygeal space to the lumbosacral joint. The opioid epidural analgesic therapy reported here was considered to be efficient to treat the painful condition of the donkey, but it was not able to completely abolish the pain.