Mourinho started just three members of his regular first-team squad: Alvaro Morata, Esteban Granero and 'keeper Antonio Adan.
But Real Madrid came out guns blazing as Lucas Vazquez scored in the ninth minute, Denis Tcheryshev 30 minutes later and Esteban Granero two minutes after that.
Matar Diop Martins gave Oviedo a spark of hope when he scored six minutes after the break, but Argentine Angel Di Maria promptly doused it with goals in the 56th and 74th minutes.
'Los blancos' take on Benfica in a second friendly Friday before heading to the United States to continue their pre-season.
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