Real Madrid's Raphael Varane has joined Gareth Bale and Keylor Navas on the injured list for Wednesday's Champions League fixture against Tottenham, but Isco has been named in the travelling squad despite missing training on Monday.
Varane picked up an adductor muscle issue in Sunday's shock 2-1 La Liga defeat at Girona, with Isco also suffering a thigh problem late in the game.
Ex-Tottenham winger Bale and Navas will also miss the trip to Wembley, with neither having recovered from their respective injuries in time.
Confirmation of the absences came before Zinedine Zidane's side flew out to London for a game which could decide who tops Group H and is seeded in the round of 16.
Madrid and Tottenham both have seven points from their opening three Champions League fixtures and drew 1-1 at the Santiago Bernabeu a fortnight ago. A win for either side will all but secure passage to the round of 16 regardless of the result in Wednesday's other Group H clash between Borussia Dortmund and Apoel Nicosia.
Nacho Fernandez should start in place of Varane in central defence, while 18-year-old Achraf Hakimi is expected to deputise again for the unvailable Dani Carvajal at right-back, with Kiko Casilla in goal in place of Navas. Should Isco miss out, Marco Asensio or Lucas Vazquez could come into the XI.
Zidane could give more team news at his pregame news conference at Wembley later on Tuesday.
Madrid's defeat at Girona on Sunday saw them drop eight points behind leaders Barcelona in La Liga, and has led to questioning of the motivation and strength in depth of the squad.