Jared Payne and Sean O'Brien will be assessed on Saturday before they can be confirmed in Ireland's side to face Australia, says assistant coach Andy Farrell.
Ireland had already made four changes to their side from the one beaten by New Zealand last weekend, with the uncapped Garry Ringrose coming into the side for the injured Robbie Henshaw.
Payne was named in the centre for the clash at Aviva Stadium, while O'Brien occupied a place in the back row of Joe Schmidt's pack.
Neither took part in the captain's run on Friday, however, and Farrell revealed both are further injury doubts for an already depleted Ireland squad.
"We've had a couple of guys that's had a couple of niggles, and the captain's run is normally just a stretching-legs type session," said Farrell.
"We made a couple of decisions this morning to rest Jared Payne and Sean O'Brien and see how they are in the morning [Saturday].
"We'll have a discussion in the morning about their situation. They both have just lower-limb tweaks, that's what normally happens during the week.
"You pick things up on the way from the game, through the week and so on.
"The main session was yesterday and we decided to give a couple of players more time.
"We've kept Peter O'Mahony here, and we've got Rory Scannell as well covering for Jared Payne.
"All the main work's been done already, that's why we are resting them, to give them every chance to feel 100 per cent."
Farrell is adamant the concerns regarding Payne and O'Brien have not affected Ireland's preparations, though, and he is confident they are ready for the Wallabies.
"No, it hasn't [distracted us], because this is what we've been building for the last year," he added.
"We've been building strength in numbers, strength in depth is getting bigger and better all the time.
"We've seen that across the last year and on the South Africa tour and we're seeing it again."