BACKGROUND: Sensorineural hearing loss (SNHL) is a common feature in the postasphyxial syndrome in newborns. Several anesthetic drugs have been proposed to attenuate secondary neuronal injury elicited by hypoxia-ischemia. We hypothesized that propofol anesthesia reduces auditory impairment after perinatal asphyxia in comparison with isoflurane. METHODS: Twenty-three pregnant ewes were randomized to propofol or isoflurane anesthesia and sedation. The lambs underwent in utero umbilical cord occlusion (isoflurane n = 5; propofol n = 7) and were compared with sham-treated animals (isoflurane n = 5; propofol n = 6) at a gestational age of 133 d. For 8 h after delivery by cesarean section, repeated auditory brainstem responses (ABRs) were recorded to obtain hearing thresholds, peak amplitudes, latencies, and interpeak latencies. RESULTS: Significantly elevated mean thresholds, diminished amplitudes, and elevated latencies were observed in the asphyxia group relative to the control group through the observation period. Comparison of anesthetic treatment in the asphyxia group revealed a significantly lower elevation in threshold and less impairment in the ABR amplitudes and latencies during propofol anesthesia as compared with isoflurane anesthesia. CONCLUSION: Our results support the hypothesis that anesthesia with propofol has a preventive effect on the functional changes to the auditory pathway in the event of perinatal asphyxia.