Conor Murray and Rob Kearney have been ruled out of Ireland's Six Nations clash with England on Saturday so Kieran Marmion and Jared Payne come into the side along with Iain Henderson.
Murray took a knock to his shoulder during the defeat against Wales last Friday which ended Ireland's hopes of regaining the title and the scrum-half will play no part in Dublin.
Fly-half Jonathan Sexton was passed fit after suffering a head injury during the 22-9 loss to Rob Howley's men in Cardiff.
Marmion will make his maiden Six Nations start at the Aviva Stadium, while fit-again full-back Payne features for the first time in the tournament in the absence of Kearney, who will undergo a scan after suffering a knee injury.
Henderson gets the nod in the second row ahead of Devin Toner, who is joined by the uncapped Andrew Conway on the bench.
Luke McGrath has also been named among the replacements to offer cover at scrum-half as Ireland aim to deny the champions a record 19th consecutive win and another Grand Slam.
Ireland: Jared Payne, Keith Earls, Garry Ringrose, Robbie Henshaw, Simon Zebo, Jonathan Sexton, Kieran Marmion; Jack McGrath, Rory Best, Tadhg Furlong, Donnacha Ryan, Iain Henderson, CJ Stander, Sean O'Brien, Jamie Heaslip.
Replacements: Niall Scannell, Cian Healy, John Ryan, Devin Toner, Peter O'Mahony, Luke McGrath, Paddy Jackson, Andrew Conway.