Jason Peters, the Eagles' 38-year-old left tackle, is headed for Injured Reserve with a foot injury.
Peters missed practice Wednesday and Thursday with an illness and returned Friday. According to Rapoport, he felt discomfort in his foot during that practice and an MRI revealed a significant injury.
NFL Network's Ian Rapoport first reported the news.
The injury is apparently unrelated to Peters leaving the field for the last two plays against the Bengals Sunday. Eagles coach Doug Pederson said that was due to "fatigue," although Peters was also checked out after the game for a leg injury.
Peters was replaced for the last few plays against the Bengals by former rugby player Jordan Mailata, who is expected to make his first career start on Sunday against the 49ers.
Mailata has played 20 career snaps on offense, 18 at right tackle in the opener and two on Sunday at left tackle.
Peters must miss at least three games. He'd be eligible to return Nov. 1 against the Cowboys.
Only three weeks into the regular season, Peters is the fifth offensive lineman the Eagles have lost to a serious injury this year.
Pro Bowl right guard Brandon Brooks is out indefinitely after blowing out his Achilles, left tackle Andre Dillard is out for the year with a torn biceps, left guard Isaac Seumalo is on Injured Reserve with a knee injury and right tackle Lane Johnson missed most of training camp and the season opener with an ankle injury that required surgery.
The Eagles will presumably start — left to right — Mailata, Matt Pryor, Jason Kelce, Nate Herbig and Johnson on Sunday.
This is the first time since at least 1950 — as far back as available records go — that the Eagles will start four different offensive lines in their first four games.
Mailata will be the fourth Eagles offensive lineman to make his first regular-season career start this year, following Jack Driscoll, who started the opener at right tackle, Herbig and Pryor.
Healthy backups currently on the 53-man roster are Driscoll, recent acquisition Jamon Brown and Sua Opeta, who has never played in an NFL game.
The Eagles have center Luke Juriga, an undrafted rookie, and rookie 6th-round tackle Prince Tega Wanogho on the practice squad.
Peters, a 9-time Pro Bowler, returned to the Eagles this summer to play right guard after Brooks got hurt and agreed to move to left tackle when Dillard got hurt if he got a pay raise.
Peters missed nine games in 2017 and three last year. He's the oldest starter in Eagles history.
Currently on IR for the Eagles in addition to Peters, Dillard and Seumalo are Vinny Curry, Dallas Goedert, Will Parks, Josh Perkins, Jalen Reagor and Quez Watkins.
The Eagles have also ruled out Alshon Jeffery (December foot surgery) and DeSean Jackson (hamstring). Rookie 1st-round pick Jalen Reagor is on Injured Reserve (ligament tear in thumb), and J.J. Arcega-Whiteside is doubtful for Sunday (calf), although he is making the trip to San Francisco.