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The Cowboys were up 13-0 when Romo lost a fumble when he was sacked.
Driven into the ground by Philadelphia's rookie linebacker Jordan Hicks, Romo clutched his left shoulder as he lay on his back.
He remained down as the Dallas offense and Eagles defense departed the field, eventually rising and making his way to the locker room under his own steam.
After X-rays, he reappeared on the sideline with his left arm in a sling.
"I'll be back," vowed Romo, who is expected to miss at least eight weeks. "But it's going to take a little bit of time."
It's another serious injury blow for the Cowboys, who expect wide receiver Dez Bryant to be sidelined until late October after breaking his foot last week in their season-opening win.
Romo missed the last 10 games of the 2010 campaign with a broken collarbone.
He said he knew right away he had a similar injury.
"I felt it, and it had a bit of a 'pop' to it," he said. "Obviously, I felt it before.
"Stuff happens, it's the NFL," added Romo, who missed the final game of 2013 with a back injury that required surgery and missed one game last year with two fractures in his back.
"The NFL is really about adversity and how you handle it," he said.
Romo wasn't the only star signal-caller hurting on Sunday.
The Chicago Bears' Jay Cutler completed his first eight passes against the Arizona Cardinals then threw an interception and suffered a hamstring injury in a vain tackling attempt.
He missed the rest of the game -- a 48-23 Cardinals win -- and it was unclear how long he might be sidelined.
"Guys have to step up when guys go down," backup quarterback Jimmy Clausen said. "That's the situation we're in right now."
New Orleans veteran Drew Brees acknowledged he was feeling it in his right shoulder after a second-quarter sack in a 26-19 loss to the Tampa Bay Buccaneers.
But Brees downplayed the chance of longterm repercussions.
"I'd say it affected me on a few of the throws down the field," Brees said. "They just didn't come out very well. ... That's the season. Everybody's dealing with something."
Detroit Lions quarterback Matthew Stafford underwent rib and chest X-rays after taking multiple hits in a 26-16 loss to the Minnesota Vikings.
He never left the game.
"There's no questioning his toughness. He's one of a kind in that regard," Lions coach Jim Caldwell said.