Andres Iniesta picked up a minor thigh injury during Spain’s 6-0 friendly win over Poland on Tuesday night.
The Barcelona player was taken off in the 39th minute of Spain’s 6-0 victory over Poland on Tuesday.
“As he wasn’t comfortable, we made the change – it’s a minor muscle injury,” said Dr Oscar Celada.
Iniesta, who missed the latter part of La Liga season because of a thigh problem, helped set up Spain’s first two goals in their World Cup warm-up.
Spain coach Vicente Del Bosque said the attacking midfielder “came off as a precaution” after feeling the twinge in his leg.
The 26-year-old, who has not played a full 90 minutes for Spain since February 2009, is set to be examined again later on Wednesday.
“We will calmly carry out tests, but we can initially rule out any muscle tear. It’s a minor injury, but we have to take precautions,” Dr Celada added.
Injury aside, it was an impressive performance from the European champions, with Alonso adding a third in the 51st minute before Fabregas scored with his first touch after coming on as substitute.
Fernando Torres replaced David Villa midway through the second period for his first appearance since undergoing surgery on his right knee in April.
“The injury has passed and now I’m able to help my team-mates, so it’s time to enjoy it,” said Torres.
“Tomorrow (Wednesday) I’m sure there will be a lot of optimism and euphoria but we know it will be difficult.”
Spain depart for South Africa on Thursday and will begin their campaign against Switzerland on 16 June before facing Honduras and Chile in Group H.