Daniel Sturridge has been ruled out of England’s Euro 2016 qualifier with Lithuania on Friday with a hip injury.
The Liverpool striker, 25, also misses the friendly against Italy in Turin on Tuesday, 31 March.
Sturridge sustained the problem during Liverpool’s 2-1 Premier League defeat by Manchester United on Sunday.
His absence could pave the way for Tottenham’s Harry Kane to make his debut at Wembley for the Group E leaders.
Sturridge’s Liverpool team-mate Adam Lallana is out of the England squad after suffering a groin injury against Louis van Gaal’s side.
Sturridge had been hoping to make his first England appearance since September when he played in the 1-0 friendly victory over Norway.
Since then, injury has forced him to miss all of England’s Euro 2016 qualifiers – against Switzerland, San Marino, Estonia and Slovenia – as well as the friendly against Scotland.
The England medical team took the decision to rule him out on Monday evening, having assessed the striker following the squad’s arrival at St. George’s Park on Monday.
Sturridge scored the hosts’ consolation against Manchester United at Anfield, but afterwards complained of discomfort in his hip.
Uncapped Kane, captain Wayne Rooney and Arsenal’s Danny Welbeck are alternative forward options.
England lead qualifying Group E by six points thanks to a 100% record in their first four games.
The top two countries qualify automatically for the finals in France next summer.
Roy Hodgson’s side face Italy in Turin on Tuesday, 31 March.