Andrews tweaked his back in Wednesday's practice and missed the next two days. Winston Justice will start for Andrews.
"Neither our people nor Shawn feels like he can make it through this game," Eagles coach Andy Reid said on Friday.
Eagles left guard Todd Herremans (foot) also is out of Sunday's game and Nick Cole gets the start.
Andrews, making the transition from guard to tackle, said this week his back felt good and he was ready to play. Instead, he's forced to sit out another game in a career that's been plagued by injury and a battle with depression.
Andrews declined through a team spokesman to comment. The Eagles have yet to play with their expected starting offensive line, which has been racked by injury.
"I told you before, does it worry me that they haven't played in a game? Yeah," Reid said. "I would've liked to have them play in a game. At the same time, if there's a position that you can work fast, as close to game speed as you can get every day, it's the O- and D-line."
Andrews, Philadelphia's first-round pick in 2004, is one of the more perplexing players in the Eagles locker room.
He missed all of training camp in 2008 with depression. He sports an orange mohawk and can usually be heard singing a pop music tune in the locker room. Andrews also posted various YouTube videos where he wears sunglasses and rambles about his latest musical compositions, which he calls his true passion. He wrote a song, "Gettin' My Michael Phelps On," which he dedicated to the Olympic champion.
The Eagles signed Andrews' brother, Stacy, and his college teammate, Jason Peters, to round out a revamped offensive line and make him feel more comfortable.
His absence this week opens the door for Justice, and for Eagles fans to try and put the memories of his first and only NFL start behind him.
It was 2007 when Justice filled in for an injured Tra Thomas against Osi Umenyiora, Michael Strahan and a Giants defense that would eventually lead them to a Super Bowl win. Umenyiora had six sacks and the Giants tied an NFL record by sacking Donovan McNabb 12 times during a 16-3 victory.
Justice has not gotten another shot at the starting lineup until now.
"I'm not even thinking about that game," Justice said. "I'm looking toward the Panthers right now and being a great offensive tackle."
Reid said on Friday that Justice has the opportunity to win the starting job away from Andrews.
"I thought one of the real positives coming out of camp was Winston Justice and how he played," Reid said. "I thought it was valuable, valuable experience that he got in there."
Justice likely will line up against Tyler Brayton, but could also face pass-rusher Julius Peppers in selected spots.
Might be a good time for fantasy owners to pick up that Panthers defense.
With such a vulnerable offensive line, Reid worked out former right tackle Jon Runyan on Thursday. Runyan never missed a game in nine years with the Eagles, starting 192 straight regular-season contests. He wasn't re-signed after having microfracture surgery on his right knee.
Reid said Andrews' injury had nothing to do with bringing in Runyan.
"I'm not going to get into how he looked and all of that," Reid said. "I just wanted to make sure that I saw him firsthand."