Jamie Osborne, Jacob Stockdale, Tadhg Furlong and Ryan Baird have been ruled out of Ireland’s autumn finale against Australia.
Versatile Leinster back Osborne and Ulster wing Stockdale sustained groin and hamstring issues respectively during Saturday’s 52-17 win over Fiji.
Prop Furlong has not featured at all this month due to a hamstring problem, while lock Baird suffered a head injury in his country’s 22-19 victory over Argentina on November 15.
Speaking about Osborne’s injury, Ireland forwards coach Paul O’Connell told a press conference: “He’s a big loss.
“He’s very versatile on the bench obviously, he covers so many different positions and is growing and getting better all the time.
“It’s a shame he’s out. Hopefully it’s nothing too serious and he’s back to us soon.”
Saturday’s Dublin showdown with Joe Schmidt’s Wallabies will be Ireland’s final match before head coach Andy Farrell takes a break to lead next year’s British and Irish Lions tour of Australia.
The Six Nations champions began November with a 23-13 loss to New Zealand before returning to winning ways against Los Pumas and Fiji.
O’Connell also confirmed Connacht hooker Dave Heffernan, Leinster prop Jack Boyle and Ulster back-rower Nick Timoney have been released to their provinces.
Former Ireland boss Schmidt, who replaced Eddie Jones as Australia coach in January, will return to the Aviva Stadium seeking a response to his side’s 27-13 defeat to Scotland.
The Wallabies won 42-37 away to England and 52-20 against Wales before Sunday’s setback at Murrayfield.
“He’s an excellent coach,” O’Connell said of New Zealander Schmidt, who led Ireland to three Six Nations titles and a historic first win over the All Blacks between 2013 and 2019.
“You cannot not work hard in a Joe Schmidt team. You’ll have a plan and you’ll know inside out how to deliver that plan.
“When you have a team of good, talented players that is half the battle: be really clear on what your plan is and be really clear on how to deliver that plan, and Joe does that really well.
“You can see with this Australian team flashes of improvement all the time. To go to Twickenham and score as many points as they did, to play the game in the way they did, to keep coming back the way they did shows where their belief and resolve has gotten to.
“There will always be days like Scotland for every team. For us it is a big challenge and part of that is knowing what they bring because Joe has coached us before.
“We know how clear he can be and that clarity allows players to play with a lot of intent and a lot of physicality, so it is a big challenge.”