It's been a very disappointing season for Ronald Koeman's side so far.
Going into the game, Barca are seventh in the La Liga table having won just four of their opening eight games.
Regardless of their problems off the pitch, that's simply not good enough for a club of Baca's size.
Thus, it's a massively important game for Barca and they desperately need all three points against their fierce rivals.
But who should start for Barca?
Andres Iniesta is still playing football in Japan with Vissel Kobe.
He's been keeping track of his former club's progress though and he shared the XI he would play against Real on Sunday. View his XI below...
ANDRES INIESTA'S XI (FORMATION: 4-3-3)
GK: Marc-André ter Stegen
RB: Oscar Mingueza
CB: Gerard Pique
CB: Eric Garcia
LB: Jordi Alba
CM: Sergio Busquets
CM: Frenkie de Jong
RW: Sergino Dest
LW: Memphis Depay
ST: Ansu Fati
With Ronald Araujo suffering from a hamstring injury, Iniesta thinks Garcia should partner Pique in the centre of defence.
Iniesta prefers to start the duo ahead of Clement Lenglet and Samuel Umtiti.
The Barca legend thinks that Mingueza should start at right-back ahead of his former teammate, Sergi Roberto.
With Pedri unavailable, Iniesta has gone with a midfield three of Busquets, De Jong and Gavi.
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While he thinks Dest, who is primarily a right-back, should play in a front three with Fati and Depay.
It's a lineup that has gone down well with Barca fans. View some reaction to Iniesta's preferred XI below...
Time will tell whether Iniesta's lineup will look similar to Ronald Koeman's.
Regardless, the Dutchman needs a result against Real - or he could well lose his position as Barca manager.