Ellis Genge was ruled out of England's Six Nations opener with Italy with a foot injury hours before kick-off in Rome, the RFU said on Saturday.
The 28-year-old prop's place on the replacements bench is taken by Bath's Beno Obano, who is in line to win his fourth cap should he come on.
The RFU gave no further information on Genge's condition, nor for how long he would be out of action.
England have not won the Six Nations championship since 2020, but are hoping to build on their surprising third place at last year's World Cup and be genuine title contenders this time round.
Teams (15-1)
Italy
Tommaso Allan; Lorenzo Pani, Juan Ignacio Brex, Tommaso Menoncello, Monty Ioane; Paolo Garbisi, Alessandro Garbisi; Lorenzo Cannone, Michele Lamaro (capt), Sebastian Negri; Federico Ruzza, Niccolo Cannone; Pietro Ceccarelli, Gianmarco Lucchesi, Danilo Fischetti
Replacements: Giacomo Nicotera, Mirco Spagnolo, Giosue Zilocchi Andrea Zambonin, Edoardo Iachizzi, Manuel Zuliani, Stephen Varney, Federico Mori
Coach: Gonzalo Quesada (ARG)
England
Freddie Steward; Tommy Freeman, Henry Slade, Fraser Dingwall, Elliot Daly; George Ford, Alex Mitchell; Ben Earl, Sam Underhill, Ethan Roots; Ollie Chessum, Maro Itoje; Will Stuart, Jamie George (capt), Joe Marler
Replacements: Theo Dan, Beno Obano, Dan Cole, Alex Coles, Chandler Cunningham-South, Danny Care, Fin Smith, Immanuel Feyi-Waboso
Coach: Steve Borthwick (ENG)
Referee: Paul Williams (NZL)