Sergio Ramos will miss Real Madrid's clash with Shakhtar Donetsk in the Champions League while Eden Hazard's fitness is improving as he nears a comeback from injury.
Los Blancos captain Ramos took a knock to his knee in Saturday's shock 1-0 La Liga loss to Cadiz and was absent from Tuesday's training session ahead of the club's opening European fixture of the 2020-21 campaign at Santiago Bernabeu.
With the first Clasico of the season against Barcelona taking place on Saturday, head coach Zinedine Zidane said he was unlikely to risk exacerbating the issue.
"There's an issue with Sergio Ramos, he hasn't trained with the team," Zidane told a pre-match news conference on Tuesday.
"We won't take any risks with the players; the players have to be fit. He's got a knock, we have to wait and see how he feels, it's true today he didn't train at the same tempo as his team-mates."
While Ramos is a fresh injury concern, forward Eden Hazard – whose time at Madrid has been blighted by fitness woes – remains a longer-term absentee.
The Belgium international, who is yet to feature this campaign, was set to return to action last month but sustained a muscle complaint during his recovery from an ankle injury.
Offering an update on Hazard, Zidane said: "Eden has been back out on the training pitch but that injury was a bit more than we hoped.
"He's in good hands and hopefully shortly he'll be back and he'll stay fit and hopefully he'll be able to play for the full season without further setbacks."
Madrid were well below their best against Cadiz, mustering just two shots on target despite having almost 75 per cent of the possession.
Zidane's side have scored just six goals in five La Liga games, but the coach, while accepting his team deserved the criticism that came their way, said there will be plenty of peaks and troughs in a busy campaign.
"I think we deserved the criticism as published following that defeat, but now it's our opportunity to turn the tide, turn that corner and hopefully you'll see a different Real Madrid," he said.
"I think whenever things have been tough, this team have stepped up and produced the goods. There are moments during the season when there are dips in form.
"The other day we could have done things better and I'm convinced we can do things better.
"I think you have to look at the bigger picture. If you look at not just us, others too, no clubs have started in brilliant fashion, teams have struggled. There will be days when we do things very, very well."