Wayne Rooney has withdrawn from the England squad and will return to Manchester United for treatment on a knee injury, the Football Association has confirmed.
The 31-year-old sat out training on Monday due to the problem and interim boss Gareth Southgate later confirmed the captain would not start the friendly against Spain at Wembley on Tuesday.
Ryan Bertrand was also absent from that session but has since been declared fit for the visit of Julen Lopetegui's side.
"Wayne Rooney has left the England squad and returned to Manchester United," an England statement read.
"The striker sat out this morning's session at Tottenham Hotspur's training ground as a precaution due to a minor knee injury.
"However, with Gareth Southgate already set to rest his captain for the visit of Spain to Wembley Stadium tomorrow night, Rooney has been allowed to return to his club for further assessment.
"Left-back Ryan Bertrand, who also missed today's session, will remain with the Three Lions squad and stays in contention for the fixture against Julen Lopetegui's side."
The news could be a blow for United manager Jose Mourinho, whose side take on Arsenal in the Premier League on Saturday.
Zlatan Ibrahimovic is suspended for that game, meaning Rooney - who has been on the fringes of the first team in recent weeks - had been likely to play a part against Arsene Wenger's side.