Spain and Barcelona midfielder Gavi suffered a serious knee injury in the Euro 2024 qualifying win over Georgia.
The 19-year-old landed awkwardly after jumping to control the ball, and left the pitch in tears in Valladolid.
Manager Luis de la Fuente said Spain must wait for tests amid concerns it could be an anterior cruciate ligament injury.
"This is the ugly part of football. This is the most bitter victory I have ever experienced in my life," he said.
"It is a very difficult moment for Gavi, Barcelona, the national team and for me - it seems as if we have lost the game.
"I am very sorry (for Gavi). Let's wait for the tests to confirm the extent of the injury."
Spain, who had already sealed their place at next summer's European Championships, beat Georgia 3-1 to finish top of Group A above Scotland.
Defender Robin le Normand put Spain ahead after four minutes but Khvicha Kvaratskhelia equalised.
Ferran Torres restored Spain's lead in the second half before Luka Lochoshvili scored an own goal for Georgia.
"We can't celebrate as we would have liked. Gavi's injury is a hard blow. I'm really gutted," said Le Normand.
Torres, who held up Gavi's shirt to celebrate his goal, said: "An important victory to end on a good note, but we leave with a bittersweet feeling.
"We don't know the extent of the injury but, knowing how much of a warrior Gavi is, we think it could be serious."