Real Madrid star Toni Kroos is set join Marcelo in the treatment room when Los Blancos visit Alaves on Saturday (23 September) after suffering a rib injury.
The news is a fresh concern for Zinedine Zidane as Karim Benzema, Theo Hernandez, Jesus Vallejo and Mateo Kovacic are also ruled out for the visit to Mendizorroza due to various injuries.
Kroos, 27, missed the last weekend's 3-1 victory over Real Sociedad due to a fitness problem.
The Germany international returned to Zidane's starting line-up for Wednesday's 1-0 defeat to Real Betis and was able to complete the full 90 minutes.
However, it looks like Kroos suffered a recurrence of the problem in that game after Real Madrid revealed on Friday morning that the midfielder skipped the final training session before Los Blancos' trip to Vitoria.
Zidane himself later confirmed the blow in a press conference, adding that he expects the midfielder to recover in time for the crucial Champions League trip to Borussia Dortmund on Wednesday night (26 September).
"He felt discomfort in his ribs again after the game and we didn't want to take any risks. I hope it's nothing serious and he'll be able to play on Tuesday. He's in a bit of pain today and the match is tomorrow – we're not going to risk it," the Real Madrid boss said in the press conference ahead of the trip to Alaves.
"Injuries are always frustrating for a coach but there's nothing we can do about it. That can happen over the course of a season and we have to deal with it. We lost the last game and we want to change things. That's the good thing about football, we've got another game tomorrow and we want to play well and win it."
Marcelo was also expected to miss the game with Alaves after being forced off in the 72nd minute of the defeat to Betis.
"Following tests carried out on Marcelo at the Sanitas La Moraleja University Hospital, he has been diagnosed with a grade 2 tear in his left bicep femoris muscle. His recovery will be monitored," the club confirmed.
The Real Madrid boss may therefore need to cover the left-back position with the versatile Nacho, as Theo is also ruled out after picking up a shoulder injury against Real Sociedad.
Meanwhile, the trip to Alaves will come too early for Karim Benzema, Jesus Vallejo and Mateo Kovacic, despite the first two returning to some light training earlier on Thursday.
One way or another, Real Madrid cannot drop more points after the latest defeat to Real Betis left them seven points behind leaders Barcelona after only five La Liga games.
Furthermore, Alaves are currently at the bottom of the table, having lost the opening five games of the season without finding the net.