The first attack happened on Thursday when swimmer Christian Einfeldt was seriously injured after a sea lion bit him on the arm.
Mr Einfeldt believes the animal followed him as he swam from San Francisco beach to the mouth of a cove.
When he turned to swim back, the large mammal was “right there”, he told local TV station KGO.
“I did feel threatened. I did have warning. But I was a quarter-mile from shore. There was nothing I could do,” Mr Einfeldt said.
When the sea lion approached, Mr Einfeldt splashed water on it but the animal did not go away, said Matthew Reiter with the San Francisco Police Department’s Marine Unit.
“When it didn’t work, he yelled at it and then the sea lion came up and bit him on the arm,” Mr Reiter added.
Mr Einfeldt started steadily bleeding and knowing he could not swim back he flagged down a sailboat which pulled him aboard. He was later transferred to hospital where he had at least two operations.
The next day, another man was bitten in the groin area as he swam in the waters off the city’s Maritime National Historic Park.
Park spokesman Lynn Cullivan said it was “a very serious bite” and the man was taken to a hospital.
The cove hosts swimming and rowing clubs and is a favourite spot for dedicated swimmers. It is usually a transit area for sea lions heading to Pier 39, where they congregate.
The aggressive behaviour is so unusual for sea lions that officials think the same animal attacked both swimmers.
More from US
US Marine ‘planned Christmas Day terror attack on San Francisco’
Elon Musk’s SpaceX rocket lights up sky leaving Californians puzzled
President Trump signs $1.5tn tax overhaul into law
UK joins UN vote to reject Donald Trump’s recognition of Jerusalem as Israel’s capital
In sea sickness and in health: Couple stage underwater wedding
Miss America chief executive urged to quit over email scandal
“It could just be a sea lion being territorial, or it could be an injured or sick mammal,” Mr Cullivan said.
“People think the bay is their backyard, but it really is the beginning of the wilderness. There is wilderness out there.”