Brian O'Driscoll and Sean O'Brien will miss Ireland's clash with England at the Aviva Stadium on Saturday through injury.
O'Driscoll suffered a 'stinger' to his shoulder in the 26-22 defeat by France in Dublin last weekend and has been omitted as a precautionary measure.
"Brian picked up a knock against France. He's running around outside, but it was prudent to us not to put him into a contact situation on Saturday," said coach Declan Kidney.
"He has made good progress, especially over the last 24 hours. With the game coming this week and a full tournament coming up, it just wasn't prudent to put him in the mix.
"I don't have the actual medical term for the injury. He gets stingers around this area (pointing to his shoulder). Sometimes you just need to rest it up and get them out of the system."
Ireland's preparations for the World Cup have also been hit by the loss of O'Brien, their most consistent performer since the start of the RBS 6 Nations.
The European player of the year sustained a knee problem midway through the second half against Les Bleus, but Kidney is unconcerned by his fitness, saying: "Sean will be fine, it wasn't prudent to include him this weekend. But as you can see he's in training already and he'll work his way back in."
Keith Earls replaces O'Driscoll at outside centre to form a midfield partnership alongside Gordon D'Arcy, with Ronan O'Gara and Eoin Reddan named at half-back.
Tommy Bowe makes his first appearance of the summer on the right wing after recovering from a foot problem, while Geordan Murphy starts at full-back after Rob Kearney, who was sidelined last weekend with a groin strain, was ruled out once again.
Hooker Jerry Flannery makes his first start of the summer following three substitute appearances, while there is a summer debut for David Wallace. The loss of O'Brien will be keenly felt, but the return of Stephen Ferris at blindside for his first start in eight months is welcome.