Brees was nearly perfect in passing for 339 yards and a season-high four touchdowns, including one to Gates, as the San Diego Chargers routed the Buffalo Bills 48-10 on Sunday for their third straight win.
Gates, a star tight end who causes headaches for defensive coordinators, sprained his right foot at the end of a 21-yard reception midway through the third quarter when he was tripped up by Angelo Crowell and then had safety Lawyer Milloy land on him. The Chargers (6-4) aren't sure how long Gates will be out.
By the time Gates was hurt, the game was well in hand and Brees had thrown scoring passes to four different receivers.
Buffalo (4-6) is now winless in five road games.
"It seemed like nothing was going our way," quarterback J.P. Losman said. "That's just the way this game is. That's what makes the wins so enjoyable, because you know how bad it feels to lose like this."
Brees completed 17 of his first 18 passes and was 28-of-33 overall, hitting eight different receivers. He said the only time he's had a better game was when he threw for five touchdown passes against Oakland last year.
"I felt really good out there," said Brees, who had two throwaways, one drop "and two I could have been a little more accurate in passing. You can always get better.
"We were doing what we feel like we can always do," Brees said. "I think those receivers feel like if I throw it anywhere near 'em, in their area code, they're going to catch it."
Keenan McCardell, who caught a 27-yard touchdown pass, said Brees spreading the ball around "opens some people's eyes, that there's other guys in here who can catch the ball and make plays, also. I think it makes it tough on a defense. You can't come in and game-plan just Antonio or just L.T. (LaDainian Tomlinson). You've got to game-plan the full offense."
Brees agreed, saying the Chargers "absolutely" can be productive if Gates misses time.
"One guy is not this team or this offense," Brees said.
McCardell had 88 yards on six catches to push his career total to 10,320 yards, to pass Hall of Famer Lance Alworth (10,266) for 21st place on the all-time list.
Alworth, who had his No. 19 retired at halftime, congratulated McCardell after his TD catch in the second quarter.
"That was unbelievable. I didn't know what to say," McCardell said. "I was just smiling."
Brees completed his first nine throws before Gates dropped a pass on third-and-2 early in the second quarter, and threw for 265 yards in helping the Chargers take a 35-10 halftime lead.
Brees "had an exceptional day," Buffalo coach Mike Mularkey said. "He made some great throws and guys were making some plays. I don't know many incompletions he threw, but I don't remember that many of them."
Gates caught five passes for 77 yards and one touchdown before being hurt. He has seven TD catches this year. Gates had a sensational 2004 season, leading the Chargers with 81 catches for 964 yards and setting an NFL record for tight ends with 13 touchdown catches. He was voted an All-Pro and selected for the Pro Bowl.
Gates missed a season-opening loss to Dallas as he finished serving a three-game suspension, his punishment for missing a team-imposed deadline for ending his training camp holdout.
The Chargers had TDs on five of their seven first-half possessions.
LaDainian Tomlinson scored on a 1-yard dive over the pile on fourth down on the game's opening drive, and it was all Brees after that.
Gates, covered by cornerback Jabari Greer, caught a 27-yard TD pass late in the first quarter. Brees had second-quarter scoring throws of 23 yards to Eric Parker, 2 yards to fullback Lorenzo Neal -- also on fourth down -- and 29 yards to Keenan McCardell.
Buffalo's Willis McGahee, who contends he's the NFL's best running back, was held to 39 yards on 10 carries.
Tomlinson, generally considered the NFL's best back -- if not the league's best player -- had 67 yards on 19 carries, and caught three passes for 22 yards. His backup, Michael Turner, had an 8-yard TD run in the fourth quarter.
- Chargers TE Justin Peelle sprained a shoulder.
- Nate Kaeding kicked field goals of 28 and 38 yards for the Chargers in the second half. Rian Lindell kicked a 53-yarder for the Bills in the first quarter.