Real Madrid coach Carlo Ancelotti will deploy Asier Illarramendi in midfield in place of the suspended Isco and the injured Sami Khedira for Saturday's La Liga game at home to Celta Vigo, the Italian said on Friday.
Isco was sent off in last weekend's 2-1 win at his former club Malaga, while Khedira suffered a concussion in Tuesday's King's Cup game against Cornella.
Fellow midfielder Luka Modric, Ancelotti's first choice alongside Toni Kroos in the middle, is also out injured and not due back until the New Year.
Illarramendi has not lived up to expectations since joining from Real Sociedad in July last year but has a chance to impress as Real seek to extend their club-record winning streak to 18 matches in all competitions, stretching back to a 2-1 reverse to champions Atletico Madrid in September.
Ancelotti told a news conference he was expecting a tough challenge from eighth-placed Celta, who surprised Barcelona 1-0 at the Nou Camp last month and secured a 2-2 draw at Atletico's Calderon stadium in September.
"They are a very aggressive side with players who work hard on the pitch," Ancelotti said.
"They will play a very intense match and it won't be an easy game," he added.
"Isco is on very good form but his absence will not affect us tomorrow because I have a lot of confidence in Illarra."
Real are two points clear of second-placed Barcelona, who host city rivals Espanyol on Sunday, after 13 matches, with Atletico in third, a further two points adrift, ahead of their game on Saturday at Elche.
"Things are going well at the moment and I have a very good relationship with the players," said Ancelotti, whose side are through to the last 16 of both the Champions League and the King's Cup.
"We fight together and we have the same goals. I want to keep it going for a long time.
"We don't need to set a limit and we have to take each match at a time. I am convinced that with this squad we will quickly get over any adversity."