The British and Irish Lions fly-half sat out training at the start of the week in Ireland's warm-weather camp in Portugal.
The Leinster playmaker has been recovering from a thumb sprain but Ireland had hoped he would be ready to feature against England.
Ross Byrne will start at fly-half and has a big chance to state his case for World Cup selection, with Joey Carbery's ankle ligament problem threatening to rule him out of the tournament in Japan.
Ireland have rolled out most of their big guns to face England, with Rory Best back as captain in a potent pack including the first-choice back-row of Peter O'Mahony, Josh Van Der Flier and CJ Stander.
Jean Kleyn wins his second cap at lock, the South Africa-born Munster star handed another chance to prove his World Cup worth.
Ireland team to face England
R Kearney, J Larmour, G Ringrose (all Leinster), B Aki (Connacht), J Stockdale (Ulster), R Byrne (Leinster), C Murray (Munster), C Healy (Leinster), R Best (Ulster, capt), T Furlong (Leinster), I Henderson (Ulster), J Kleyn, P O'Mahony (both Munster), J Van Der Flier (Leinster), CJ Stander (Munster).
Replacements: S Cronin (Leinster), J McGrath (Ulster), A Porter, D Toner (both Leinster), T Beirne (Munster), L McGrath (Leinster), J Carty (Connacht), A Conway (Munster).
