In December, UEFA ruled Malaga would be ineligible to play in Europe for two years, later reduced to one, for violations of financial fair play rules.
Malaga appealed to CAS last week, but UEFA's ruling has been ratified.
A CAS statement read: "CAS has dismissed the appeal filed by Malaga against the decision taken on December 21, 2012 by the Adjudicatory Chamber of the UEFA Club Financial Control Body decision.
"As a consequence, the Spanish club is excluded from the UEFA Europa League 2013/14 and will have to pay a fine of 300,000 euros."
Malaga's place in next year's Europa League will provisionally go to ninth placed Sevilla.
Rayo Vallecano, who finished eighth, would have taken the spot but have not been granted a UEFA licence.