Real Madrid playmaker Isco withdrew on Sunday from the Spain squad for Tuesday's friendly away to Russia in preparation for next year's World Cup due to a thigh injury.
On his return to his native Malaga, Isco was given a standing ovation as he limped off 25 minutes from time in Saturday's 5-0 thrashing of Costa Rica after a reckless challenge from Kendall Watson.
"The medical services of his club, who have been informed by the doctors of the national team, will be the ones who will assess the treatment that the player must follow from now," the Spanish Football Federation said in a statement.
Isco, 25, who has been a shining light in an otherwise disappointing season so far for Real, now faces a race against time to be fit for Saturday's derby at city rivals Atletico Madrid.
Arsenal striker Olivier Giroud will miss Tuesday's friendly against world champions Germany in Cologne due to injury, the French football federation said on Sunday.
Giroud, 31, suffered a right thigh strain during Friday's 2-0 victory over Wales at the Stade de France, where he scored his 29th international goal.
France have several on-form strikers jostling to play alongside Antoine Griezmann including Anthony Martial of Manchester United or Giroud's Arsenal teammate Alexandre Lacazette.
Giroud has been granted permission to return to his club and is yet to be replaced in Didier Deschamps's squad.
- Martin O'Neill: Republic of Ireland 'might have to score two' to overcome Denmark in Dublin
- Preview: With a tie to chase Northern Ireland's road to Russia could end rather nearer the Alps
- David Ginola interview: 'I was actually dead, my heart had stopped'
Nicklas Bendtner has warned the Republic of Ireland that Denmark will be ready to go all the way to the wire to keep their World Cup dreams alive.
The Danes will arrive in Dublin on Tuesday evening having been booed off by sections of the home crowd at the Parken Stadium on Saturday night after Ireland frustrated them for 90 minutes to snatch a 0-0 draw in the first leg of their winner-takes-all play-off.
One way or another, there has to be a winner at the Aviva Stadium and Bendtner insists he and his teammates will fight to the death to secure their ticket to Russia.
The 29-year-old Rosenborg striker said: "We're going down there to try to win the match. I can't say what's going to happen, but we're prepared to play 120 minutes if that's what it takes.
"I think it will be a different match. They know that they can't play a match where they have to stay so deep. They know that they have to come out and try to score, so I think it's going to be a little bit more open.
"They will come more out, which allows us to get more space. It will be a more interesting match."