Sunday afternoon's meeting comes with Real Madrid second in the table, three points behind Real Sociedad and with a game in hand, while Barca are two points behind Real Madrid in seventh. That means that at this early stage, the result won't be decisive in the title race, but it would still be very significant for both clubs.
Although Barcelona coach Ronald Koeman survived his side's defeat to Atletico Madrid before the international break and saw them squeeze through vital games against Valencia and Dynamo Kiev, defeat to Real Madrid in the Camp Nou would put him back to square one, while a heavy defeat could make his position almost untenable.
Koeman will be without Ronald Araujo and Pedri for the game, but Eric Garcia returns after suspension and Ansu Fati, who on Wednesday (October 20) agreed a new contract until 2027, will start after only playing the second half against Dynamo.
Real Madrid coach Carlo Ancelotti had been questioned after a poor run of form before the break, but his side's 5-0 win away to Shakhtar Donetsk will have eased some pressure, while the return of Ferland Mendy and Marcelo give him more options in defence for a game which Eden Hazard will miss with another muscle problem, Xinhua reports. The round of matches kicks off this weekend with fifth-placed Osasuna at home to Granada, who have not played in three weeks after last weekend's match against Atletico Madrid was postponed to allow Atletico's South American players recovery time after their international commitments.
Granada coach Robert Moreno remains under pressure and could lose his job if his side lose.
Athletic Bilbao's match at home to Villarreal will be their first game in 22 days after they also didn't play last weekend to help accommodate Real Madrid.
Villarreal travel to Bilbao unbeaten away in La Liga and after a 4-1 win away to Young Boys in the Champions League, but will have to rotate their side after the midweek game.
Valencia look to end a run of five games without a win when they entertain Real Mallorca, while there is a tense game between Cadiz and Alaves.
Alaves have suffered seven defeats from eight games to pile the pressure on coach Javier Calleja, while Cadiz's defeat to Espanyol last weekend leaves them with just seven points from nine games.
Espanyol travel down the east coast to face Elche and they will hope in-form Raul de Tomas can break down Fran Escriba's well-drilled side, who have only netted six goals all campaign.
Sunday kicks off with Sevilla at home to Levante, who are looking for their first win of the season with their second coach of the campaign after Javier Pereira replaced Paco Lopez.
Real Betis face Rayo Vallecano in the first of a series of games which will test the visitors, who are currently sixth after a flying return to La Liga. Radamel Falcao will be back for Rayo after being rested last weekend.
League leaders Real Sociedad, who are still without the injured Mikel Oyarzabal, travel to play Atletico Madrid in what would be the standout game on any other weekend of the season. Atletico lost to Liverpool in the Champions League on Tuesday and also lost Manuel Llorente to injury.
The round of games ends on Monday (October 25) when Quique Sanchez Flores aims to steer Getafe to their first win of the season at home to Celta Vigo, who need striker Iago Aspas to recover his best form and whose coach Eduardo Coudet could face the sack if his team return to Galicia empty handed.