Jacob Stockdale, Tadhg Furlong, Ryan Baird and Jamie Osborne have been ruled out of Ireland's final autumn international against Australia on Saturday.
Ulster wing Stockdale (hamstring) and Leinster full-back Osborne (abductor) were forced off during Saturday's win over Fiji.
Speaking about Osborne's injury, Ireland forwards coach Paul O'Connell said: "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."
Leinster lock Ryan Baird was ruled out of the Fiji game with a head injury while prop Tadhg Furlong has missed the entire autumn campaign with a hamstring issue.
O'Connell also confirmed that Dave Heffernan (Connacht), Nick Timoney (Ulster) and Jack Boyle (Leinster) have been released back to their clubs before the United Rugby Championship's return this weekend.
After bouncing back from a defeat by the All Blacks with wins over Argentina and Fiji, Ireland host Joe Schmidt's Wallabies at Dublin's Aviva Stadium at 15:10 GMT on Saturday.
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