The 21-year-old was initially called up for the two-legged tie but will now miss out due to injury.
Gravenberch sustained the injury during Liverpool's Carabao Cup final defeat to Newcastle United on Sunday. The club confirmed his withdrawal in a statement, though the severity of the issue has not been disclosed.
Despite Gravenberch's absence, Liverpool will still be represented in the Dutch squad, with captain Virgil van Dijk and forward Cody Gakpo both included. The Netherlands will be hoping to advance past Spain as they aim for Nations League success.
"Ryan Gravenberch has left the Oranje's training camp this evening," the official Netherlands account stated via X.
"The midfielder is still suffering from an injury sustained over the weekend that prevents him from playing in the matches against Spain. Take care, Ryan!"
Liverpool released a statement regarding the injury: "Ryan Gravenberch has departed the Netherlands camp and will not be involved in their fixtures this week.
"The Liverpool midfielder had linked up with his country, alongside Cody Gakpo and Virgil van Dijk, for a UEFA Nations League double-header versus Spain on Thursday and Sunday.
"However, the Dutch announced on Wednesday evening that Gravenberch has now withdrawn from duty due to a fitness issue.
"The 22-year-old will be assessed upon his return to Merseyside, with the Reds back in action when they host Everton in the Premier League on April 2."