California sea lions have been historically difficult to anesthetize. Most routine procedures, such as taking blood and doing physical examinations can be carried out using physical restraint on healthy sea lions that weigh under 75 kg. Small sea lions, under 50 kg can usually be managed by two experienced handlers. One handler wraps a towel around the head, and pushes the head to the ground, while the other handler straddles the sea lion, and firmly holds both front flippers the animal's sides. A third handler may be needed to hold the rear flippers of the animal.

Larger sea lions will need to be restrained using a "bull pole" or a long pole with a loop of rope at one end. The loop is placed over the head of the animal, and quickly twisted snugly around the neck. Two bull poles are sometimes necessary to restrain stronger animals. Once the head is controlled, a blanket can be thrown over the head, and one or two people can restrain the front flippers. Sea lions that are very large, usually over 150 kg will need to be forced into a squeeze cage designed for pinnipeds.

Sea lions that cannot be restrained or require a more involved procedure must be anesthetized. For elective procedures, plan to anesthetize the animal when the weather is cool. Try to weigh the animal. The margin of safety is small when using injectable anesthetic agents in sea lions. Fast the animals for at least 12 hours. Pre-anesthetize using 0.02 mg/kg atropine IM. Wait for ten minutes. Give 1.7 mg/kg Telazol (1: 1 tiletamine/zolazepam) IM. It is best to use freshly reconstituted Telazol, however Telazol may be used if it has been reconstituted within 7 days of the procedure, and kept refrigerated. The drug usually takes 2 to 12 minutes to take effect. Be prepared to intubate the animal immediately, as about 10% of sea lions anesthetized with Telazol stop breathing. If the initial does of Telazol is inadequate, Do Not Give More Telazol. The procedure must be aborted, or you must try to complete the anesthesia using isoflurane or halothane gas. A Telazol anesthesia lasts an average of 22 minutes from the time the drug takes effect to the time the animal is too active to complete most procedures. Most sea lions can rise onto their front flippers within an hour of the Telazol injection. Always have plenty of ice on hand to keep the animals cool. Longer procedures require intubation and maintenance on isoflurane. Monitor animals for at least four hours after the procedure to ensure that they do not overheat.