Luka Modric and Dani Carvajal have been cleared to face Atletico Madrid on Saturday as Real Madrid seek a much-needed lift in the title race.
With LaLiga leaders Barcelona heading to Leganes earlier in the day, Madrid could be 11 points off the summit by the time the derby at Wanda Metropolitano kicks off.
But the reigning champions have been boosted by the return to fitness of influential midfielder Modric and full-back Carvajal, who did not go on international duty with Spain following a viral pericardium infection.
"Modric had a scare yesterday, but trained normally today," coach Zinedine Zidane said on Friday. "He is ready to play.
"Dani has been ready for a long time. He was not with the national team because it was better to stay here and work."
One player who will not be involved in the first derby at Atletico's new stadium is Gareth Bale, with the Welshman having suffered a strained adductor muscle.
However, Zidane is confident Bale will be back at full strength soon, possibly as early as next week.
"He's a player who wants to be fit, to help his team," said Zidane. "He's the one who is most upset with what has happened.
"He will come back better than ever, that's what I think, that's what I believe. Everyone will have their own view on this, but he'll come back better than before.
"Hopefully next week he'll be back at 100 per cent."
Atletico won when the sides last met in May, but the 2-1 result still saw them dumped out of the Champions League semi-finals 4-2 on aggregate.