Ireland captain Caelan Doris has been ruled out of the Nations Championship Southern Series along with Tommy O'Brien.
They picked up injuries during and have been replaced by Ulster's uncapped brothers Bryn and Zac Ward.
Doris was forced off at Croke Park with a foot injury, with O'Brien suffering a a groin complaint.
They will miss matches against Australia on July 4, Japan on July 11 and New Zealand on July 18.
Andy Farrell's squad depart for Sydney on Monday, with Leinster hooker Dan Sheehan leading the side for the three-match tour.
Farrell, who , had already suffered a string of injuries to key players with Jack Crowley, Andrew Porter and Mack Hansen all ruled out.
Crowley, who had re-established himself as Ireland's starting fly-half during the 2026 Six Nations, had missed the end of the season with Munster because of an obscure nerve issue in his leg.
Porter and Hansen had also suffered injury-hit campaigns.
The IRFU confirmed a further seven players were unavailable due to injury: Ryan Baird, Shayne Bolton, Jack Boyle, Edwin Edogbo, Tom Farrell, Paddy McCarthy and Calvin Nash.
