While on international duty with Spain, Ramos came off the bench for just four minutes against Kosovo when the match was already won in order to continue tallying up his caps.
The decision to do this has had consequences for Real Madrid, though, as he missed the Champions League fixture against Liverpool during the week and will miss the Clasico, too, while there are doubts as to whether he will make it back for the return quarter-final leg versus the English champions.
Raphael Varane also missed the Liverpool game due to a positive coronavirus test, and he remains absent due to his self-isolation.
Zinedine Zidane had to put out a makeshift back four in the Champions League with Lucas Vazquez at right-back, Nacho and Eder Militao in the centre, and Ferland Mendy on the left.
The foursome performed excellently, though, and Zidane will likely go with them again against Barcelona.
Fede Valverde played a few minutes against Liverpool but he probably isn't fit to start here, which will mean a midfield trio of Casemiro, Toni Kroos, and Luka Modric, all of whom were fantastic against Liverpool.
Eden Hazard might make the bench on Saturday, but he won't be fit enough to replace Marco Asensio, Vinicius Junior, or Karim Benzema, the starting trio from Tuesday.
For Barcelona, Gerard Pique is still fighting for fitness but this fixture will probably be too early for him, meaning a back three of Oscar Mingueza, Frenkie de Jong, and Clement Lenglet should continue.
Ronald Koeman will likely not make many, if any, alterations from the Barca XI that defeated Real Vallaolid 1-0 on Monday.
That means Sergio Busquets partnering Pedri in the middle of midfield with Sergino Dest and Jordi Alba as the wing-backs.
In addition to Pique, the Blaugrana continue to be without Ansu Fati, Neto, and Philippe Coutinho.