Fernando Torres is a major doubt to face his former club Atletico Madrid in the UEFA Champions League next week.
The Liverpool striker limped out of Spain's win in Belgium after just 16 minutes and was visibly upset.
The injury is to his right leg with conflicting reports in Spain about whether it is his hamstring or thigh. If it is the former, then it may be the same injury he sustained against Aston Villa earlier in the season which saw him ruled out for two weeks.
Initial reports in Spain suggest that the injury, although not serious, is likely to sideline him for 10 days - which would rule him out of Saturday's home meeting with Wigan in the Premier League and the return to Atletico, his former club.
Spain boss Vicente del Bosque admitted Torres was upset with the injury.
"I am very sad for Torres," he said. "This is undoubtedly a very big blow for him."
Spain team doctor Oscar Celada confirmed Torres left the field in some distress.
"He has intense pain in the back part of the thigh," said Celada.
"It is difficult to diagnose now exactly the extent, if it is a question of a strain or a small tear.
"If it is a strain then he could be out for about a week."
Torres' Liverpool team-mates Xabi Alonso and Alvaro Arbeloa admitted losing the striker, who has started the new Premier League season in fine style, is a big blow.
"For us it is undoubtedly bad news for both the international squad and Liverpool," said Alonso.
"We have to wait and see what the tests say, but we do not stop now until around Christmas, and we have a big calendar coming up with Atletico Madrid and Chelsea, and we cannot let up.
"It is not the first time this has happened for him with the national side, and it is a blow to have an injury when he is in such a good streak of form."
Arbeloa added: "It is bad news to have a new muscle injury at a time like this.
"We hope it is nothing too serious and hope he will soon be playing for Liverpool because he is very important."
Torres is now almost certainly out of the weekend Premier League clash with Wigan at Anfield, but it remains be seen whether he has enough time to recover for the Atletico clash.
Further bad news for Liverpool boss Rafa Benitez came from Scandinavia as Ryan Babel limped out of Holland's win against Norway after just 26 minutes.
As yet the Dutch authorities have not confirmed the extent of the injury to the forward.