At about 11:30 p.m., officers responded to a report of a possible homicide at the school, located at 400 Murchison Drive.
Officers arrived and found the victim suffering from multiple wounds. He was pronounced dead at the scene, police said.
Kirk Black, spokesman for the San Mateo Union High School District, said the victim was apparently stabbed near the on-campus tennis courts. He said the tennis courts abut a public skate park and bicycle path that is a gathering place for youth.
Black said he does not know if the death occurred on school property or just off it.
Investigators say there were witnesses to the killing and are conducting interviews this morning.
The suspects are two men. One is described as a Samoan male about 18 or 19 years old, 6 feet 2 inches tall and 130 pounds. He was wearing a black hooded sweatshirt, a white T-shirt, black shorts and low-top shoes.
The other suspect is described as a Pacific Islander man between 22 and 23 years old, 6 feet 1 inch tall and 180 pounds with a muscular build.
He had a black beard and was wearing a beanie, a vest and black hooded sweatshirt, black pants, basketball shoes, and was carrying a backpack, according to police.
The victim's name is being withheld pending notification of his family.
Black said police have cordoned off the area this morning to conduct their investigation. He said the incident is not affecting the school, which is out for the summer. Classes are scheduled to resume Aug. 16.