Castleford half-back Rangi Chase has been ruled out of England's autumn internationals after picking up a groin injury during their training camp in South Africa.
The 2011 Man of Steel complained of the problem during last week's high-altitude camp in Potchefstroom and a scan has ruled him out of the games against Wales in Wrexham on Saturday and France at Hull KR's MS3 Craven Park a week later, as well as the November 11 final if England get there.
"It is a great shame," coach Steve McNamara said. "He has trained hard during our camp and has been an integral member of the squad."
He added: "The lad is devastated to miss out. He was looking forward to the month ahead with England and making a huge impact.
"The important thing now is for him to rest, rehabilitate and get himself ready for the new season. He has a big 12 months ahead and can be part of our World Cup aspirations."
England's chief medical officer Dr Chris Brookes said: "Although Rangi's injury is responding to treatment, it has been decided that this improvement has not been sufficient for him to participate in the tournament.
"The England Rugby League medical staff will continue to monitor his progress and rehabilitation to ensure he is fully recovered from this injury."
McNamara will select his team for the Wales game from a reduced 23-man squad, but has not ruled out bringing in a replacement during the tournament.
"I do have the option, if I desire, to bring in an extra player, but at this stage I don't envisage adding to the 23 now that Rangi is out," he said.
England also look certain to be without Wigan full-back Sam Tomkins for the opener as he continues his recovery from a knee injury, while his club-mate, hooker Michael McIlorum, still has one game left of a three-match suspension to serve. Both could return for the game against France, who opened the tournament with a 20-6 victory over Wales in Lens on Saturday.
- Rangi Chase