ORCHARD PARK, N.Y. -- Bills rookie quarterback EJ Manuel was ruled out from playing against the Miami Dolphins because of swelling in his left knee.
That means journeyman backup Thad Lewis, who is from Miami, will make his fourth start of the season on Sunday -- and second of the year against the Dolphins.
The Bills (5-9) have already been eliminated from playoff contention. The Dolphins (8-6), meanwhile, control their own playoff destiny. Miami, which has won three straight and four of five, can clinch a berth by either winning its final two games or having both Baltimore and Cincinnati lose.
Bills coach Doug Marrone made the decision to sit Manuel early into practice on Wednesday after the rookie first-round draft pick showed difficulty with his mobility. Manuel practiced inside the team's fieldhouse, and was then held out once Marrone shifted the session outside on the slick turf at Ralph Wilson Stadium.
Marrone said Manuel's lack of mobility and instability in the knee would have made it difficult to play. And he was also concerned how ready Manuel might be with limited practice time.
Manuel was hurt during a 27-20 loss at Jacksonville on Sunday, though it's not clear on which play the injury occurred.
Drafted 16th overall out of Florida State, Manuel was the first and only quarterback selected in the first round.
He has gone 4-6 as a starter this season. And this will mark the third time since training camp that he's been sidelined with a knee injury.
Manuel missed the final two weeks of the preseason after having a procedure on his left knee, which he hurt in a game against Minnesota. He then missed four games after spraining his right knee in a 37-24 loss at Cleveland on Oct. 3.
Marrone first revealed the injury on Monday, but was optimistic about Manuel's chances of playing.
That changed over the past two days when Manuel's knee did not respond to treatment.
Though Manuel won't play this weekend, Marrone said he felt "very confident" that Manuel will start in the Bills finale at New England on Dec. 29.
The injury comes after Manuel had won his first road game of the season, and had a chance to help Buffalo string together consecutive wins for the first time since Weeks 2 and 3 of 2012.
Manuel is 3-2 at home and has struggled with his consistency on the road.
Lewis has proven to be a capable backup since being promoted from the practice squad on Oct. 7. He went 1-2 in place of Manuel earlier this season before Lewis was sidelined by a rib injury in a 35-17 loss at New Orleans.
Lewis' victory came against the Dolphins on Oct. 20, when he went 21 of 32 for 202 yards and an interception in the 23-21 win.
The Bills acquired Lewis in a trade with Detroit in August, after Manuel hurt his left knee.
He was cut by Buffalo before the start of the season and then signed to the team's practice squad.
Overall, the Duke product has gone 62 of 103 for 652 yards with three touchdowns and two interceptions.
Receiver Stevie Johnson is also not expected to play, Marrone said. Johnson has been excused to be with his family in California following the unexpected death of the player's mother on Saturday.
"I don't believe that he will be available for our game on Sunday," Marrone said. "And I think it's important we realize this tragedy, and our thoughts and prayers are with Stevie and his family."
Marrone also considered starting safety Aaron Williams' chances of playing on Sunday as "50-50." Williams did not practice after hurting his ribs while making a tackle in the fourth quarter against Jacksonville.