LaLiga had appealed against global football governing body FIFA's extension to the international window for World Cup qualifiers by two days because it meant players participating in the matches would be unable to turn out for their clubs when Spain's domestic fixtures resume on Sept. 11.
While FIFA said the "decision confirms the legality of FIFA's decision," it was not clear if the CAS ruling was focused only on the admissibility of the case being launched by the Spanish league.
The organisation could not immediately provide further clarity but said it welcomed the decision by CAS.
"FIFA welcomes today's ruling by the Court of Arbitration for Sport (CAS) rejecting the Spanish LaLiga's request to set aside the decision by FIFA to extend the international window for the FIFA World Cup qualifiers in South America by two days," the statement said.
"The compromise decision to add two additional days rather than three as requested by the South American confederation CONMEBOL was taken by the competent FIFA body after consulting all relevant stakeholders and after taking into account all relevant circumstances, in particular, the challenges created by the COVID pandemic and especially health considerations for players.
"Today's CAS decision confirms the legality of FIFA's decision and entirely rejects the arguments made by Spain's LaLiga.
"On Wednesday, FIFA President Gianni Infantino called for a show of solidarity from all member associations, leagues, and clubs, to do what is right and fair for the global game. We now expect the release of players for the upcoming FIFA World Cup qualifiers in South America to occur in accordance with the recent FIFA decision, the legality and legitimacy of which has today been recognised in today's CAS ruling."
FIFA announced earlier this month that fixtures missed in March due to the COVID-19 pandemic would be played in September and October, and increased the CONMEBOL international window by two days until Sept. 10.
It cited extensive travel and player safety as the reasons for the extension.
Real Madrid, Barcelona, Sevilla and Atletico Madrid were all due to play league fixtures 24 hours later and on Thursday LaLiga said it had held a meeting with all concerned teams, who agreed not to release their players for international duty.
LaLiga criticised the CAS ruling in a statement, calling FIFA's decision a "plain declaration of intent to intervene in autonomous national leagues."
The league also responded by shifting fixtures for the corresponding weekend, moving Real Madrid vs. Celta Vigo and Espanyol vs. Atletico Madrid from Saturday Sept. 11 to Sunday Sept. 12 and requesting for Sevilla vs. Barcelona and Villarreal vs. Alaves, both set for Sept. 11, to be postponed.
The fixture change allows players involved in the World Cup qualifiers to play for their clubs but causes more disruption to the teams, who are all due to play in the Champions League the following Tuesday and Wednesday.
Information from the Associated Press and Reuters contributed to this report.