Crews responded to reports of people in the water at about 2 p.m. at 95 Harbor Master Road, according to the South San Francisco Fire Department.
Arriving police pulled from the water one male and one female victim, who were both unconscious, and started CPR. Fire officials then arrived and transported the victims to a local hospital.
One victim was listed in critical condition and the other was declared deceased after arriving at the hospital, according to fire officials.
No other information was immediately available.