On defense, star linebacker Jerod Mayo went on season-ending injured reserve Wednesday, joining star tackle Vince Wilfork on the list. On Sunday, their best defensive back, Aqib Talib, could be sidelined after hurting his hip. And just when starting tackle Tommy Kelly returns from a knee injury is unknown.
Then there's the offense.
Wide receiver Danny Amendola and guard Dan Connolly suffered concussions last Sunday. Tight end Rob Gronkowski hasn't played all season.
Gronkowski was the only one of those seven to practice on Wednesday, and he was limited.
But the Patriots lead the AFC East by two games.
"A lot of teams face challenges. It's just really how you deal with them," Tom Brady said Wednesday. "We've lost some guys, dealt with some issues, like every other team. We're handling them OK. We're 5-1. It's a decent start."
But now four of the Patriots' best players are injured on a defense that has allowed the fourth fewest points in the NFL.
Dane Fletcher, who has started five games since joining the Patriots in 2010, could start at outside linebacker for Mayo on Sunday against the New York Jets (3-3).
"Our defense knows what we have to do," Fletcher said. "It's always next man up. It's kind of that philosophy around here and whoever it may be, it's time for them to fill those shoes."
Those shoes are pretty big.
Mayo, a two-time Pro Bowl standout, has the most tackles in the NFL since 2010 and calls the defensive signals. Wilfork is a five-time Pro Bowler who has anchored the defensive line since 2005.
They're also leaders, the only two defensive co-captains on the team.
"I think of it as Mayo and Vince are still our captains," said safety Devin McCourty, a co-captain the past two seasons.
Mayo was injured in the fourth quarter of Sunday' 30-27 win over the New Orleans Saints when he and safety Steve Gregory tackled Darren Sproles. Mayo lay on the ground then reached for the upper right area of his chest. Mayo's agent, Mitch Frankel, did not respond to a request for comment on a report that Mayo had undergone surgery for a torn chest muscle.
"I just came down and made the hit," Gregory said. "I didn't know what the extent was."
Wilfork tore his right Achilles tendon Sept. 29 in a 30-23 win over the Atlanta Falcons then underwent surgery.
"When you lose someone like we did with Vince or Jerod, it's tough," Brady said, "but I'd say a lot of teams deal with it, too.
"As much as you hate to lose guys, there's nothing you can do about it and the season doesn't end. You have to keep fighting on, just as they would want us to, just like they did when I went out, just like they did when guys like Rodney (Harrison) went out. We've lost some pretty key, critical guys over the years. Ty Law got hurt at one point."
Brady had a season-ending knee injury in the 2008 opener and the Patriots went 11-5 with Matt Cassel at quarterback but missed the playoffs.
Harrison missed the last 13 regular-season games in 2005 and both playoff games with a knee injury.
Law played only the first seven games in 2004 before injuring his foot. The Patriots went on to win their third Super Bowl in four years.
"There are a lot of guys who have been injured," Brady said. "You just have to try to fill the spot and other guys have to pick up the slack."
One of them is outside linebacker Dont'a Hightower, who is expected to call defensive signals in place of Mayo.
"I'm looking forward to it," said Hightower, who has started since being drafted in the first round last year. "If something ever happened, I knew that I would have to step up and do it. I mean I'm not nervous about it. It's something that I've done before, maybe not in the NFL, but I've done it before."
Now he expects to do it again.
Mayo is done for the year.
"He does a lot for us on the field, off the field," coach Bill Belichick said, "but we're just going to have to move on."
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