The 28-year-old has left the national team's base in Nuremberg and returned to Munich, where his right knee will be assessed by the record titleholders' medical staff.
Chance for Weidenfeller or Zieler
"I would have liked to field my best team against Spain but we didn't want to take any risks with Manuel," said Germany coach Joachim Löw. "With and , we have two exceptional alternatives who have more than deserved a chance. I know I can rely on both of them."
Neuer had a rather quiet night between the sticks on Friday night, as he won his 57th cap for the four-time World Champions. He was forced into a save in each half but otherwise watched on with most of the action taking place at the other end of the field.
One of a kind
"We always want to give it our best, but it's tough when they've got the team bus parked right at the back," . "It's not easy, but it was important that we got one or two goals in the first half."
Neuer is one of six FC Bayern players on the shortlist to win the 2014 FIFA Ballon d'Or after being named the IFFHS Goalkeeper of the Year for 2013. Bayern expect him to be fit to face TSG 1899 Hoffenheim when the Bundesliga resumes on 22 November, and for the UEFA Champions League trip to Manchester City FC the following week.