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OBJECTIVE To compare the propofol infusion rate and cardiopulmonary effects during total intravenous anesthesia with propofol alone and propofol combined with methadone, fentanyl or nalbuphine in domestic chickens undergoing ulna osteotomy. STUDY DESIGN Prospective, randomized, experiment trial. ANIMALS A total of 59 healthy Hissex Brown chickens weighing 1.5 ± 0.2 kg. METHODS Anesthesia was induced with propofol (9 mg kg-1) administered intravenously (IV) and maintained with propofol (1.2 mg kg-1 minute-1) for 30 minutes. Birds were intubated and supplemented with 100% oxygen through a nonrebreathing circuit under spontaneous ventilation. Thereafter, each animal was randomly assigned to one of four groups: group P, no treatment; group PM, methadone (6 mg kg-1) intramuscularly (IM); group PN, nalbuphine IM (12.5 mg kg-1); and group PF, fentanyl IV (30 μg kg-1 loading dose, 30 μg kg-1 hour-1 constant rate infusion). During the osteotomy surgery, the propofol infusion rate was adjusted to avoid movement of birds and provide adequate anesthesia. Pulse rate, invasive blood pressure, respiratory frequency, end-tidal carbon dioxide partial pressure (Pe'CO2) and hemoglobin oxygen saturation (SpO2) were recorded. RESULTS Data were available from 58 chickens. The mean ± standard deviation propofol infusion rate (mg kg-1 minute-1) for the duration of anesthesia was: group P, 0.81 ± 0.15; group PM, 0.66 ± 0.11; group PN, 0.60 ± 0.14; and group PF, 0.80 ± 0.07. Significant differences were P versus PM (p = 0.042), P versus PN (p = 0.002) and PF versus PN (p = 0.004). Pulse rate, blood pressure and SpO2 remained acceptable for anesthetized birds with minor differences among groups. Values of Pe'CO2 >60 mmHg (8 kPa) were observed in all groups. CONCLUSIONS AND CLINICAL RELEVANCE Methadone and nalbuphine, but not fentanyl, decreased the propofol infusion rate required for anesthesia maintenance, but resulted in no obvious benefit in physiological variables.