Wentz, center Ryan Kelly and receiver Zach Pascal join two-time Pro Bowl left tackle Eric Fisher on the sideline because of health and safety protocols. Fisher tested positive for the virus last week.
Three-time All-Pro Quenton Nelson was activated Monday after multiple negative tests. Nelson was deemed a close contact to Fisher.
Coach Frank Reich planned to use this week to test Wentz and Nelson, who both had foot surgery to remove a bone fragment. Both did limited work three straight days last week and were cleared for full action this week.
"They need to be ready to go Wednesday, like the game is being played Wednesday so they can practice full on Wednesday, practice full on Thursday," Reich said on a video call Sunday.
"So, in order to get there for Wednesday and Thursday, they're going to have to do some work this week. They're going to have to prove that they can bounce back from a good day's work and follow it up with another day."
That won't happen now - at least not for Wentz, who already missed three weeks because of the injured left foot.
SEE ALSO: QB Gardner Minshew comes to Philly, but what does that mean for Eagles?
Kelly also missed three weeks with a hyperextended left elbow.
Pascal has been the Colts most consistent receiver the past two seasons when they were hit hard by injuries.
Fisher isn't expected to play until late September or early October because he's still recovering from the torn Achilles tendon he suffered in last season's AFC championship game.
While some, such as All-Pro defensive tackle DeForest Buckner and running back Jonathan Taylor, quickly acknowledged they were vaccinated when camp opened in late July, others, such as Wentz, said they wanted to keep their decisions private.
But the league's COVID-19 protocols have thrust the debate into the public realm.
Wentz, Kelly and Pascal did not test positive for the virus yet were deemed close contacts. The interpretation is they were unvaccinated.
Reich even defended Wentz when asked whether his decision to possibly jeopardize his game-day availability with more trips to the COVID-19 list was a failure in leadership.
"Carson in many ways is an exemplary leader," Reich said. "Are any of us the perfect leader? I don't know, I don't think so. We all have holes in our game somewhere and we're all trying to get better and we're all trying to learn. I'm trying to learn as a leader. This is year four as a head coach, I feel like I'm just scratching the surface of what it means to be a leader and I can get a lot better. I hope all of our players feel like that."
The loss of Wentz is the toughest blow because of his limited amount of work with his new teammates. Reich remains hopeful Wentz, who was acquired from Philadelphia in a March trade, will start the Sept. 12 season opener against Seattle. If he can't, second-year quarterback Jacob Eason would likely make his NFL debut.
SEE ALSO: What Carson Wentz said, and didn't say, about his Eagles' departure
"Jacob's handled himself like a pro," Reich said Sunday. "I think his bright spots have really been throwing the ball down the field, making some nice chunk plays down the field and I think the other bright spot for Jacob was that it wasn't too big for him. He got in there and looked comfortable, looked like he belonged."
COVID-19 has been a concern for the Colts, who have consistently ranked near the bottom of the league in vaccination rates. Reich's most recent update was that about 75% of players had been vaccinated.
The absences have hit hard.
Reich missed the first week of camp following a positive test despite being fully vaccinated. Four players - cornerbacks T.J. Carrie and Xavier Rhodes, defensive lineman Al-Quadin Muhammad and offensive lineman Julie'n Davenport - all landed on the COVID-19 list during the first week of camp.
Now three more are on it.
Wentz is one of several Colts players who declined to answer questions about vaccination status, calling it a personal decision. He did wear a mask while helping teammates on the field during his previous absence.
"We all feel that sense of we have to respect it and make good decisions to - like I said - do nothing to derail this season," he said after the first camp practice. "Everybody is in this together one way or the other and we all have to do our part to keep everyone safe."
Impact on Eagles
The Colts acquired Wentz during the offseason and reunited him with Reich by giving the Eagles a third-round pick in this year's draft and a conditional second-round pick in the 2022 draft.
The conditional second-rounder can become a first-round pick based on Wentz's playing time.
Wentz needs to play at least 75% of the Colts' offensive snaps for the 2022 conditional pick to convey to a first-rounder.
The pick also could become a first-rounder if Wentz plays at least 70% of the snaps and the Colts reach the playoffs.
Eagles coach Nick Sirianni named Jalen Hurts the starting quarterback Tuesday after weeks of declining to do so, citing the importance of creating competition at every position.
Hurts, the team's second-round pick in 2020, started four games as a rookie in place of Wentz. He completed 52% of his throws for 1,061 yards with six touchdowns and four interceptions while rushing for 354 yards and three scores.
Indy acquired offensive lineman Matt Pryor in a trade with Philadelphia on Tuesday. The Colts sent a sixth-round pick to the Eagles got a seventh-rounder back for the third-year player.
The Associated Press and ESPN contributed to this report.
The video in the player above is from a previous story.