Barca have lost on their travels to San Sebastian in each of the past three seasons.
Barca have lost on their travels to San Sebastian in each of the past three seasons and already trail Real by four points having been held 0-0 at home by nine-man Malaga last weekend.
The champions will at least benefit from having the on-fire Lionel Messi available.
Messi was badly missed due to illness against Malaga, but took his tally to 18 goals in 15 games this season with a double in a 2-0 win at Celtic that guaranteed Barca's place in the last 16 of the Champions League as winners of their group on Wednesday.
All four of Barca's slip-ups in La Liga this season have come when Messi hasn't completed the 90 minutes.
"It is a difficult game because of the team they have. They are playing very well, they are up in the European places and it is years since we won there," Messi said on Thursday.
"It will be a very tough game. We can't afford to play badly because we need to win."
A run of four straight wins, including over Atletico Madrid in their last home outing, has seen Real Sociedad rise to joint fourth in the table.
"To play against Barcelona is always an extra motivation because there are one of the best in the world and we know what it means to play against them," said the Basque side's Mexican forward Carlos Vela.
Barca will again be without the injured Andres Iniesta and Samuel Umtiti, while Neymar has to be careful as a yellow card would see the Brazilian miss the Clasico through suspension.
Barca could find themselves seven points back by the time they kick off on Sunday as Madrid host the struggling Sporting Gijon on Saturday.
Zinedine Zidane's men extended their unbeaten run in all competitions to 30 games with victory at Sporting Lisbon on Tuesday.
However, progression to the last 16 of the Champions League for a record 20th straight season came at a huge cost as Gareth Bale will have to undergo surgery on an ankle injury that is set to keep the Welshman out for at least two months.
Real should still have way too much firepower for a Sporting side that haven't won in nine La Liga games and are in the bottom three.
Madrid captain Sergio Ramos is also a booking away from missing the Clasico and may not be risked after making his return from a six-week injury lay-off in Portugal in midweek.
Toni Kroos and Alvaro Morata are also sidelined by injury, but Brazilian midfielder Casemiro could make his return after two months out with a broken leg.
Behind Spanish football's two behemoths, five clubs are separated by just four points in the battle for the other two Champions League places.
Sevilla can move provisionally above Barca into second with victory on Saturday over a Valencia side still flirting with relegation.
Valencia coach Cesare Prandelli has lamented a psychological block affecting his players after a disappointing 1-1 draw at home to rock bottom Granada left Los Che still just two points above the drop zone last weekend.
Meanwhile, Atletico Madrid will look to bounce back from a run of three league defeats in four games at another side in the relegation zone when they travel to Osasuna.
Fixtures (all times GMT)
Eibar v Real Betis (1945)
Malaga v Deportivo la Coruna (1200), Real Madrid v Sporting Gijon (1515), Espanyol v Leganes (1730), Sevilla v Valencia (1945)
Villarreal v Alaves (1100), Osasuna v Atletico Madrid (1515), Celta Vigo v Granada (1730), Real Sociedad v Barcelona (1945)
Las Palmas v Athletic Bilbao (1945)