Having secured a comfortable victory over Wales in their Autumn Nations Cup opener on Friday, Andy Farrell's Ireland head to Twickenham to face Eddie Jones' England and will do so without two key players with Jonathan Sexton and Robbie Henshaw ruled out through injury.
Ireland confirmed the news that the pair would be unavailable for selection on Monday. The likes of Jacob Stockdale and Billy Burns are also in doubt for the clash while Iain Henderson and Shane Daly are back in training.
Henderson and Stockdale were both late withdrawals from the squad to take on Wales on Friday while Burns, Henshaw and Sexton were all substituted before the final whistle.
The injuries mean that Farrell will be forced to make some changes for the clash with England. We take a look at the team he could start with against England.
15. Hugo Keenan
Jacob Stockdale's fitness will dictate who starts at fullback. If the Ulster outside back is fit he will likely start at fullback but if not, Hugo Keenan is likely to start at fullback for a second straight game.
Shane Daly could even be given a starting debut but Farrell's side will already be hugely impacted by the loss of Henshaw and Sexton while Ringrose is also sidelined so he may take a more pragmatic approach.
14. Keith Earls
The disruptions in the backline could be eased by Keith Earls return to the starting line up. The Munster has recovered from his injury and got 10 minutes off the bench against Wales.
A seasoned international, if fully fit, Earls would slot seamlessly back into the starting line and bring a calmer head. This would see Andrew Conway drop out of the side despite having a solid game against Wales where he was excellent under the high ball.
Conway could well slot in at fullback too but Farrell seems to prefer Keenan and Stockdale in that role.
13. Chris Farrell
Seems to be the most logical option in the outside centre role with Garry Ringrose and Robbie Henshaw sidelined.
12. Bundee Aki
It's highly unlikely to see anyone else start in the #12 jersey on Saturday. Stuart McCloskey is the only other inside centre in the squad and considering all the changes in the backline, Aki like Earls would bring solidity.
11. James Lowe
A strong debut against Wales and looked comfortable at test level.
Lowe would certainly be up for the test of taking on England and did little to warrant a drop.
10. Ross Byrne
While Conor Murray did well to close the game out for Ireland at flyhalf on Friday, it's extremely unlikely that Andy Farrell will entrust him to play out the entire game in the position.
That leaves Billy Burns and Ross Byrne with the rare opportunity to start a big test match on Saturday. Burns suffered a head knock against Wales and while he may be fit for the visit to Twickenham, Byrne may well get the nod.
9. Conor Murray
Jamison Gibson-Park stepped up well in his first start for Ireland against Wales but we expect Conor Murray to regain the starting jumper.
With Ireland losing Sexton, Murray will surely be recalled to the starting line up.
1. Cian Healy
Healy has been solid for Ireland recently and hasn't done anything to warrant a drop.
2. Rob Herring
Ronan Kelleher performed well against Wales but Herring may well earn a recall to the starting XV having been rested against Wales.
Heffernan or Kelleher could provide cover.
3. Andrew Porter
Undroppable at the moment. Had another strong game against Wales.
4. Quinn Roux
Farrell will certainly have options with Tadgh Beirne fit and Iain Henderson likely to be fit. However, Roux's game against Wales may just keep in the starting line up for another week.
5. James Ryan
Quickly getting back to his best. May well get there against the English.
6. Caelon Doris
A positional switch with Stander returning to the starting line up. Doris was in fine form against Wales again.
7. Peter O'Mahony (c)
Could well captain the side unless James Ryan is entrusted with the role.
Josh van der Flier or Will Connors could well be included if O'Mahony doesn't captain the side.
8. CJ Stander
Stander was in excellent form during the Six Nations and his abrasive carries and work at the breakdown could be key for Ireland.