This study compared the effects of drug combinations commonly used for chemical restraint of southern elephant seals. The combinations were: ketamine and diazepam, ketamine and midazolam, ketamine and xylazine, and tiletamine and zolazepam. The main aims were to gather basic information regarding the response of the animals to the different combinations, and to determine which were most useful for routine chemical restraint. All drug combinations could be used safely although apnea and whole-body shaking occurred with each. There were significant differences in several of the responses measured. Poor muscle relaxation and prolonged apnea were associated with ketamine and diazepam use. Animals given ketamine and xylatine were more depressed, took longer to recover, had a higher incidence of thermoregulatory problems, and lower heart rate than after other combinations. Ketamine and midazolam and tiletamine and zolazepam produced fewer complications than the other drug combinations, and tiletamine and zolazepam showed greater predictability of response and ease of use, making it preferable for use by people with little experience in anesthesia of elephant seals.