It is also an encounter which may theoretically be the last between the two clubs for each club captain.
The deals for both Messi and Ramos expire on 30 June and they have each theoretically been free to speak to other clubs since January.
The future of both players remains unclear, but Madrid boss Zinedine Zidane is in no doubt that he would like to see both players sign on their respective deals.
Zidane told reporters at his pre-match press conference, as per Marca: “I don’t want it to be Messi’s last Clásico, I want him to stay at Barcelona. He’s fine there. It’s good that he stays for La Liga.
“We know the player that Messi is. He may not be scoring goals, but we know the player that he is. We are going to play against Barcelona. It is true that we know the player that he is, but they are all very good – they have many great players.”
Zidane was then asked in his press conference about the issue dominating Real Madrid news, the future of Ramos: “Hopefully it is not his last Clasico and he stays here.”