Flegler would have been assured a spot in Billy Slater's Maroons side for the third match of the series on July 12, having started in Queensland's Origin II masterclass after earning selection on the bench for the opener.
Instead, the 23-year-old will begin rehabilitation on a Lisfranc (midfoot) injury suffered in Sunday's loss to Gold Coast and cross his fingers for a speedy recovery.
Brisbane have confirmed Flegler will miss this Saturday's local derby against the Dolphins, and while they are yet to reveal a hard-and-fast timeline for his return to the field, the type of injury he has sustained typically takes at least three weeks to heal.
The third Origin match will be played at Sydney's Accor Stadium in little more than a fortnight.Â
If Flegler requires surgery, he could miss the remainder of the season.
"Fleg has a Lisfranc injury in his foot, and we will see a specialist in coming days to decide on the best option for treatment," Broncos head of performance Dave Ballard said.
Flegler's injury is set to test the Maroons' front-row depth, with South Sydney enforcer Jai Arrow also unavailable with an ankle injury.
Melbourne captain Christian Welch could be in line for a Maroons recall after being named as 19th man for Origin I, or Slater could choose to blood Raiders hitman Corey Horsburgh, who filled the same role in the second game of the series.
Broncos second-rower Riki is due to consult with a specialist after picking up a plantar fascia injury in the loss to the Titans.
He is likely to miss six-to-eight weeks, or longer if he requires surgery.
"Both players will miss this weekend's game and we will take on board the medical advice before sorting out what the weeks ahead look like in terms of rehab for Jordy and Tom," Ballard said.
The pair's injuries also have ramifications for the second-placed Broncos as they look to bounce back to form and avoid the late-season fade that cruelled their finals hopes last year.
Brisbane are already without important forward Kurt Capewell, who suffered a quad injury at training last week, and will lose star fullback Reece Walsh to a three-match suspension incurred for swearing at referee Chris Butler in round 17.
"I know Reece will be remorseful of his actions," said Broncos veteran Martin Taupau.
"Reece is a young kid, he's got a lot of energy. He knows what he needs to fix and he's on it."
One of the forwards charged with lifting amid Riki and Flegler's absences, Taupau admitted losing two more players during the already busy Origin period was not ideal.
"It was pretty tough hearing that news this morning. It's also not an ideal time to have those types of injuries," Taupau said.
"It's a great opportunity for the next lot of middles to be able to step up and fill in their shoes.
"No matter who you are, what position you play, whether you're medical staff or admin staff, we're all ready. We prepare for this sort of stuff."
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