Spain will be without Chelsea's Alvaro Morata, Barcelona's Andres Iniesta and Real Madrid's Dani Carvajal for their final two World Cup qualifiers against Albania and Israel.
Morata and Iniesta suffered muscular injuries while playing for their clubs over the weekend, while Carvajal has been sidelined with a heart problem.
Coach Julen Lopetegui has called up Athletic Bilbao forward Aritz Aduriz, 36, to replace Morata.
Aduriz last featured for Spain in a 2-2 friendly draw with England in 2016 and has scored four goals in seven league appearances for Athletic this season.
Lopetegui has also added two uncapped players, Real Sociedad right-back Alvaro Odriozola and Las Palmas winger Jonathan Viera, to his squad.
"The three players have been selected by Julen Lopetegui and will join the team in training on Monday afternoon," a Spanish Football Federation (RFEF) statement said.
Morata, who has six goals in seven Premier League games for Chelsea, was injured in the home defeat to Manchester City while Iniesta, who came on as a substitute against Las Palmas, felt pain and could be out of action for 10 days.
Morata's absence is a blow for Spain, with the 24-year-old their joint-top scorer in qualifying, alongside Diego Costa and David Silva, on five goals.
Costa, who has yet to play this season, was again omitted. He returned to Atletico Madrid from Chelsea last month but cannot play until January.
Spain are unbeaten in qualifying and are three points clear of Italy at the top of Group G.