Wagner did not practice this week because of the knee sprain he suffered on the first play of Seattle's blowout win over the Detroit Lions last week.
"He's got some swelling and it just didn't loosen up enough," coach Pete Carroll said. "He's got a tight knee so he can't do it. If he could, if there was any way, he would. He can't."
Last week, Wagner acknowledged his uncertain future in Seattle, answering in the affirmative when asked if he has wondered if he'll remain with the team in 2022 given his huge cap number of $20.35 million. His tune was different on Wednesday, when he said he has "a lot of optimism" that he'll be back.
Carroll was asked Friday if he has the same optimism.
"I would love Bobby to play here forever," Carroll said. "He's been as solid as you could ever want a player to be and we've kind of grown up as Seahawks together here in this program over the years and I'd love for him to be here. I don't see why we'd be thinking anything else."
Wagner is an eight-time Pro Bowl selection and has made a strong case this season to be named a First Team All-Pro for the seventh time. He was leading the NFL in tackles with 170 -- which broke his own franchise record -- and hadn't missed a snap this season until he hurt his knee last week.
Wagner, 31, also owns the Seahawks' all-time tackles record.
He can make up to $16.6 million in 2022, the final year of the three-year, $54 million extension he negotiated himself in 2019. None of that $16.6 million is guaranteed.
While speaking last week about his uncertain future, Wagner said there will "obviously" be changes on the heels of a down Seahawks season that no one saw coming. They've suffered double-digit losses for the first time since 2009. Wagner added that he doesn't know whether he'll be part of those changes.
Cody Barton will start at middle linebacker Sunday in his absence.
The Seahawks also ruled out right tackle Brandon Shell (shoulder) and cornerback John Reid (concussion). Tight end Will Dissly (heel), right guard Gabe Jackson (knee) and defensive end Carlos Dunlap (ankle) are listed as questionable.
Carroll said the team has had to manage Jackson's knee in practice all season and that it's "a little bit worse than it's been." He and Dissly will be game-day decisions, per Carroll.
He said defensive end Alton Robinson should be activated off the COVID-19 list Saturday.