Starting free safety Charles Godfrey suffered what coach Ron Rivera called an Achilles injury on his right foot in the third quarter. Starting strong safety Quintin Mikell suffered an ankle injury severe enough he left with a boot cast.
Starting left cornerback Josh Thomas suffered a game-ending concussion early in the second quarter.
There's a chance all three could miss next weekend's game against the New York Giants.
But even before and after the injuries the secondary, which gave up the league's worst opponent completion percentage a year ago, looked suspect. Seattle's Russell Wilson completed 76 percent of his passes for 320 yards last week in a 12-7 victory.
Buffalo rookie EJ Manuel completed 27 of 39 pass attempts for 296 yards, including a game-winning 2-yard toss to a wide-open Stevie Johnson with two seconds remaining.
The last play left cornerback Captain Munnerlyn, the only starter that escaped injury, almost speechless as he sat in front of his locker.
"How to sum it up?'' Munnerlyn said. "We had the game. He had zero timeouts, eighty yards to go, they drove all the way and scored a touchdown.
"Ain't too much you can say. Keep working on Monday. Feel better.''
But can the Panthers feel better about their chances with second- and third-string players to an already suspect group on the field? It's hard to imagine no matter how good the defensive front seven is playing.
"It was a tough day for us,'' strong safety Mike Mitchell said. "That's why it's so important for every guy to be ready to play. I'm trying to choose my words carefully. It's tough. It was tough.''
It won't get any easier.
"I'd say the morale is definitely down,'' said defensive end Greg Hardy, who went without a sack for the second straight game after setting his goal at 50 during the preseason. "The good thing is we've got a lot of games left and a lot of great guys even with the injuries.
"We're going to be more motivated than we are down. We just have to make sure the morale stays up and the guys stay together.''