Bale, who was forced off injured in Real's last two Liga games against Atletico Madrid and Alaves, is also a doubt for the UEFA Nations League match away to Ireland on October 16
Wales forward Gareth Bale will miss the chance to face Spain and his Real Madrid team mates including Sergio Ramos and Nacho in an international friendly on Thursday after coach Ryan Giggs said he had been ruled out through injury.
Bale, who was forced off injured in Real's last two Liga games against Atletico Madrid and Alaves, is also a doubt for the UEFA Nations League match away to Ireland on October 16.
"Gareth has got a little bit of muscle fatigue and he won't be involved against Spain," Giggs told a news conference on Wednesday ahead of the game at the Principality Stadium.
"We don't want to take any risks and we are monitoring it every day. Playing in Spain he wants to be a part of it but first and foremost health comes first. We want a fit and raring to go Gareth Bale."
Bale has had a bad run of injuries since he joined Real in 2013, although he has been fit for most of this year.
The 29-year-old came off at halftime during the 0-0 draw with Atletico last month but no injury was detected in a scan carried out by Real, although the Welshman did miss last week's 1-0 Champions League group stage defeat by CSKA Moscow.
Bale returned against Alaves on Saturday but asked to be substituted in the 80th minute.
Giggs said it was touch and go whether Bale could play against Ireland, but predicted he would be ready for Real's game against Levante when La Liga resumes on Oct. 20.
BREAKING: Gareth Bale has been ruled out of Wales vs. Spain pic.twitter.com/jYkY30C8ZR— B/R Football (@brfootball) October 10, 2018
"I'd say he's 50-50 at the minute for the Ireland game," said Giggs, whose side are second in Nations League B group four, level on three points with leaders Denmark and above bottom side Ireland on none but having played a game more.
"He had a scan last week, a couple of weeks ago with Real Madrid. We rescanned it and have done everything we can to get as much information," said Giggs.
"There was a little bit on both scans - but there's always something. We're treating the symptoms but it's nothing to worry about. Either way, I expect him to be fit for Madrid's next game."