The Spaniard is unable to lift his sock because of an infected pimple.
Asensio is believed to have suffered the unfortunate problem after shaving his legs.
Real boss Zinedine Zidane has confirmed the problem and the bizarre reason for the 21-year-old missing tonight’s match at the Bernabeu.
“He has a pimple on his leg which means he cannot lift his sock,” he said.
Real are looking to win the Champions League for the third season in a row.
As well as Apoel, they will face Tottenham and Borussia Dortmund in Group H.
Asensio has enjoyed a good start to the season, netting four goals in Real’s opening six games of the season.
And Zidane will hope the starlet can return for the La Liga clash with Real Sociedad on Sunday.