Ireland centre Garry Ringrose was on Saturday ruled out of the British and Irish Lions' first Test against Australia, with English hooker Luke Cowan-Dickie also a doubt as both men deal with concussions.
Lions head coach Andy Farrell said Ringrose failed a head injury assessment following their midweek win against the ACT Brumbies in Canberra.
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"Garry, unfortunately, had a delayed reaction. He had headaches for a day and it carried on the next day," said Farrell.
"So he went through concussion protocols and failed those. So unfortunately for Garry and for us, he needs 12 days so that puts him out for the first Test.
"He's playing very well, but you don't mess around with these things."
The Lions have plenty of other options at centre already in the squad, including Bundee Aki, Huw Jones, Sione Tuipulotu and Owen Farrell.
The tourists produced their best rugby in Australia so far in a 48-0 canter against a makeshift Australia-New Zealand XV in Adelaide, crossing for eight unanswered tries.
But the win was soured when Cowan-Dickie was stretchered off after taking a knee to the head and suffered a concussion.
Later, Cowan-Dickie's fellow England front-rower in Jamie George was called up to the squad having trained with the set-up in Dublin before they left for Australia.
The experienced George withdrew from England's starting line-up hours before kick-off of their second international with Argentina in San Juan.
George, 34, was twice a Lions tourist in 2017 and 2021, and on Sunday will head to Brisbane -- the location of the opening Lions Test.
While the injuries are a setback, Farrell was pleased with their "professional" performance against Les Kiss's invitational side.
"We played a nice controlled game of rugby and never let them in the game," he said.
"We stayed at it. It was never going to be perfect. We kept going as a team and that's the main thing.
"Very pleased to finish off what's been a tough enough block for all sorts of reasons to get to this point now," he added. "Really proud of everyone.
"It's nice to get a good performance then roll into a Test series in a nice shape as a squad in regards to where our game is at, our mentality and how much we've got to improve."
