Striker Wayne Rooney injured an ankle in training on Friday and will miss England's friendly against Austria next week and their Euro 2008 qualifier against Croatia on November 21.
Just hours after the Manchester United striker was named in England's squad for those matches, his club announced on their web site (www.manutd.com) he had damaged his ankle in training and would be out for up to four weeks.
It is the second serious injury Rooney has suffered this season after breaking a bone in his foot on the opening day of the campaign which kept him out of five United matches and three England internationals.
Since recovering in September he has been in outstanding form, scoring seven goals for United in his last seven games and two more for England in his last two internationals.
Although Rooney will miss England's next two games, former skipper David Beckham is set to win his 98th and 99th caps after being recalled to Steve McClaren's squad on Friday after injury.
Beckham, hoping to become only the fifth England player to play 100 times for his country, is fit again after recovering from a knee ligament injury suffered with his LA Galaxy side in August that has kept him out of England's last four games.
England face Euro 2008 co-hosts Austria in Vienna in a friendly next Friday and then host Croatia in their final Euro 2008 Group E qualifier at Wembley Stadium on Nov. 21.
Croatia top the group with 26 points and have two matches to play. England have 23 points with one match to play and Russia 21 points with two to play.
If Russia beat Israel and Andorra in their remaining two matches, they will qualify, even if England defeat Croatia at Wembley.
McClaren said he was still optimistic England would qualify for next year's finals in Austria and Switzerland.
"The main disappointment is that it is out of our hands," he told reporters at a press briefing in Yarm, northeast England.
"But I always believed the game against Croatia would be the decider and I still think that. Russia have to go to Israel -- a proud nation with a great home record and we hope they get a result against Russia. The pressure is on Russia.
"Croatia still have to go to Macedonia and that is not an easy game. I still believe the Croatia game at Wembley will be the decider."
McClaren, who flew to Los Angeles to check on Beckham's fitness last week, said: "His fitness is fine, his injury is fine and he is included in the squad because although he hasn't played many games recently he is a big game player.
"With John Terry and Rio Ferdinand out of the squad we are lacking experienced players."
Skipper Terry, who is recovering from knee surgery, is some weeks away from fitness and was omitted from the squad, as was suspended Manchester United centre-back Ferdinand.
Chelsea defender Ashley Cole was recalled after nearing fitness following the ankle injury he sustained in the qualifier against Estonia on Oct. 13. His club mate and fellow defender Wayne Bridge is also recalled after injury.
Manchester United midfielder Owen Hargreaves is another player back after injury after missing all five of this season's England games with a knee injury.
Goalkeepers: Paul Robinson (Tottenham Hotspur), David James (Portsmouth), Scott Carson (Aston Villa)
Defenders: Wes Brown (Manchester United), Sol Campbell (Portsmouth), Ashley Cole (Chelsea), Joleon Lescott (Everton), Nicky Shorey (Reading), Phil Neville (Everton), Micah Richards (Manchester City), Wayne Bridge (Chelsea)
Midfielders: David Beckham (LA Galaxy), Shaun Wright-Phillips (Chelsea), Steven Gerrard (Liverpool), Gareth Barry (Aston Villa), Joe Cole (Chelsea), Frank Lampard (Chelsea), Ashley Young (Aston Villa), David Bentley (Blackburn Rovers), Stewart Downing (Middlesbrough), Owen Hargreaves (Manchester United)
Forwards: Michael Owen (Newcastle United), Alan Smith (Newcastle United), Peter Crouch (Liverpool), Jermain Defoe (Tottenham Hotspur).