Barcelona star Eric Garcia limped out of Spain's warm-up before Saturday evening's UEFA Nations League clash with England.
Foot Mercato report that Garcia had been named in the starting line-up at right-back, only to pull out at the last moment because of the injury.
Marc Bernal comes in to replace him from kick-off, according to the Spanish press.
Newspaper Sport report that Garcia felt pain in his left knee that stopped him playing comfortably.
How serious is it? That is now the key question, with Spain and Barcelona desperate to avoid a lengthy spell on the sidelines.
A medical statement is expected to reveal the initial assessment. Whatever it says, this is a genuine blow for club and country alike.
Spain's medical staff will decide whether Garcia stays with La Roja or heads back to Barcelona for tests.
Barcelona's medical team, meanwhile, already know about the injury and are waiting on further details.
Drawn in Group Three of League A in the UEFA Nations League, Spain face a tough test in a demanding pool.
Once this trip to Wembley to face Thomas Tuchel's England is done, Lamine Yamal and his team-mates host Croatia next Tuesday in their first home match since winning the World Cup.
Spain then welcome the Czech Republic next Saturday before travelling to face Croatia on 6 October, closing out the international break.