The Patriots don't often lose, and when they do, it's never by much. Tom Brady and the offense are starting to find their stride, and they look primed and dangerous.
But have the injuries on defense finally caught up with them? They don't have a healthy starting cornerback left.
What will the Pats have to do to regroup to face their biggest and most hyped game of the season?
Here are the takeaways.
Kenbrell Thompkins saw his snaps plummet after the loss to the New York Jets before being inactive against the Pittsburgh Steelers. Many were writing the rookie off, but Thompkins showed up against the Panthers with two catches on two targets for 60 yards.
The second of which set up the go-ahead score on the 1-yard line.
The Pats have lacked a player with big-play ability on the outside of their offense, and Thompkins delivered a couple of big plays.
The Pats offense overall was strongly balanced against the Panthers, with 25 rushes and 40 passes. Thompkins was a solid element of a versatile group that is growing harder and harder to cover.
The Patriots were excited to welcome Aqib Talib back into the mix, but things couldn't have gone much worse.
Talib seemed agitated from the outset, giving up a big play then drawing a 15-yard penalty that helped set up the Panthers' first scoring drive. Talib continued to joust with Steve Smith until getting benched for a few plays.
He would return, drawing two penalties on the game, only to leave again with a "hip" injury, likely a re-injury. He wouldn't finish the game, as a hobbled Kyle Arrington, Logan Ryan and Marquice Cole tried to stop Cam Newton.
Talib certainly didn't look like the shutdown corner, nor model citizen, that he looked like before getting hurt.
Maybe it was just an NFC South rivalry thing with Smith, but prospects are certainly not looking up with Talib heading into the Manning showdown.
A big momentum shift in the game came on Stevan Ridley's third fumble of the season, and second in the past two games.
Unlike his first in Week 1, Ridley was not benched after getting immediately strip tackled by Troy Polamalu before the Pats' bye. But against the Panthers, Ridley did take a seat for a while.
He would return and run hard like he usually does and finished the day with 13 carries for 48 yards and a long of 13 yards against a tough run defense.
Ridley has impressive burst, but his fumble problems continue, making him a frustrating player.
With LeGarrette Blount (10 carries, 49 yards) looking better each week the Pats have some insurance for Ridley, but they should continue to give him a chance to work through his problems.
Forget about "easing him in"—the Pats immediately thrust Vereen into the passing-down running back role, and he shined.
He led the team with eight catches on 11 targets for 65 yards. Vereen's burst and playmaking ability were on display from the first drive, and it's clear he will make a big difference in this offense going forward.
Despite missing his trademarked wheel fade route, Vereen looked strong in pass protection and showed no ill effects from his wrist injury.
As Vereen gets back into game shape, he'll only be more versatile and the kind of weapon the Pats lacked in the early part of the season.
Cam Newton torched the Patriots defense on multiple third downs with his legs, as the Pats simply had no one in their linebacking corps who could stick with him.
Newton finished the game with a team-leading 62 yards on seven carries. The Pats had success containing mobile quarterbacks earlier this season, but not on this night.
The Panthers finished the day 8-of-11 on third down, and if there was one reason why they lost this game, that is it. The Pats' overall lack of athleticism looked like it had caught up to them.
With their make-shift 3-4 defense they held up okay against the traditional run. No running back gained more than seven yards on any carry. It was the quarterback who gashed them, and without Jerod Mayo, Vince Wilfork and Tommy Kelly, they had no answer.
The Patriots front seven is a physical and tough—there's no denying that—but they're limited in space and only have a few blue-chippers left.
The only every-down front seven starters still playing for the Patriots are Rob Ninkovich and Chandler Jones, and they continue to both have strong seasons.
Ninkovich (two sacks, one tackle for loss, one QB hit) and Jones (one sack, one tackle for loss, one QB hit) are now the playmakers. It's hard not to wonder what kind of seasons they'd be having with elite defensive tackles beside them.
Jones now has nine-and-a-half sacks on the season and is having a breakout season, while both he and Ninkovich rank in the top five of Pro Football Focus' 4-3 defensive end run-stoppers (subscription required).
Jones and Ninkovich are the clear-cut defensive MVPs, and the Pats are happy to have both locked up for the next few years.
The Panthers sacked Brady twice in the first half but didn't get him again the rest of the game. The Patriots showed some of the protection breakdowns that have haunted them this season but remedied the situation and gave Brady a chance to get the offense going.
After a punt and Ridley's fumble, the Patriots would score on every drive the rest of the game, except the last one. The problem is that the defense only got off the field enough to give the offense seven possessions the entire game.
Brady was deadly in the second half, throwing to a variety of receivers, going back to his early-career mantra that his favorite receiver was the "open" one.
This was an excellent Carolina defense playing in their home stadium, and the Patriots offense was equal to the task. They came up 25 yards short, but as this offense continues to play together, they'll only get better.
If there's a big takeaway on the offensive side of the ball, it's that they're going to be just fine, offensive line play included. If only Ridley could just hang on to the ball.
The only thing that really matters is that the Patriots are 7-3, in first place in the division with a two-game lead. They are still in solid position to compete for a playoff bye and, with a shot at Denver in Foxborough, still hold much of their fate in their own hands.
The most looming question is at cornerback, where the Pats no longer have a starter who is healthy. They are down to Ryan and Cole, and facing Manning with those two as your starting corners is not exactly ideal.
The Patriots season could depend on getting healthy at defensive back. Will Talib ever be free of this hip ailment? Does Arrington even have a groin left to tear? There is much uncertainty, and Devin McCourty can only do so much.
The offense is showing signs of dominance again, but if the defense can't get off the field on third down, it's going to be an uphill climb every time.
If Talib can regain his early season form, Dennard bounces back from his new knee problem and Steve Gregory's thumb heals up, the Pats have a shot against anyone in the playoffs.
The only thing that's for certain is that they'll go down swinging.