The traditional curtain raiser for the league campaign is going ahead despite the players' union calling a strike for the first two weekends of the new campaign in the top two divisions.
Real and Barca, the world's two richest clubs by revenue, slugged it out an unprecedented five times last season in three different competitions.
Barcelona came out on top in the league and Champions League semi-final while Real won the King's Cup in a series of matches notable more for the increasingly acrimonious atmosphere between the clubs than for the quality of their football.
Super Cup holders Barca have eclipsed their arch-rivals over the last three years by winning two European Cups and a treble of league titles, which means this showdown is important more as a psychological indicator of the clubs' strengths.
Turkish midfielders Hamit Altintop and Nuri Sahin have been sidelined with injuries. Mourinho also has a doubt over Sergio Ramos, who pulled out of Spain's squad for the midweek friendly against Italy with a recurrence of a back problem.
Chile forward Alexis Sanchez, along with Argentine Lionel Messi, have only just returned to training after July's Copa America tournament.
Many Barca fans will be hoping the drawn out transfer saga surrounding Arsenal captain Cesc Fabregas will have been concluded by the weekend and that the club's former youth team player will at least be in attendance in the stands.
Barca's pre-season form has been patchy and they often take a while to get into their stride in a season.
"They are always very difficult games and very tense when we play against Real Madrid," Barca forward Pedro told reporters.
"We are starting the season with a difficult test but I'm sure the team will respond."
