Madrid's sluggish start combined with Barca's red-hot form has already seen Tito Vilanova's men open up an eight-point gap on the reigning champions, and a home victory on Sunday in round seven would stretch that already sizeable advantage further still.
An 11-point gap may not be impossible for Madrid to overcome, especially with so much of the campaign left, but with Barca having only lost six league games in the last three seasons, the task that would face Jose Mourinho's side should they lose is clear to see.
Barca midfielder Xavi admits the benefits of a victory for his side would be huge, but insists the Catalan giants are not getting carried away with the situation.
He said today: "It would be a seventh successive victory in the league for us and a big blow to morale for Madrid.
"It would be a very important advantage but we could still lose those points.
"Whatever happens there is still a lot of the season left. A win would give us a lot of confidence because it's our age-old rivals, and would make the league more difficult for them. They are three very important points but the league will not be decided in this match."
The Spain international added: "Regardless of the points difference anything can happen. This is Madrid. Last year we were also favourites and they won here."
Madrid's 2-1 win at the Nou Camp in April saw Mourinho's side move seven points clear of Barca at the summit, and there was no way back for the Catalan outfit after that as their three-year reign as Spanish champions came to an end.
Cristiano Ronaldo scored the winning goal in that game and he heads into this week's clash in superb form having struck hat-tricks in Madrid's last two matches against Deportivo La Coruna and Ajax.
Ronaldo has now scored 12 goals in all competitions this season, two more than his big rival at Barca Lionel Messi.
Ronaldo's form is great news for Madrid after the Portugal international created a huge stir earlier this season after revealing he was "sad" for professional reasons but without elaborating.
That incident was one of a numbers of issues that plagued Madrid at the start of the campaign, with Mourinho questioning the commitment of his players after seeing them win just one of their opening four league games despite downing Barca to win the Spanish Supercopa in the same period.
That poor form is the reason why Madrid are now playing catch-up, but victories in their last four competitive matches, as well as an 8-0 thrashing of Millonarios in the Santiago Bernabeu Trophy last week, means the reigning champions look to be finally hitting their stride.
Madrid midfielder Xabi Alonso is now looking for another triumph this weekend, saying: "It would be good to win and bad to lose, that's obvious. We know the (points) disadvantage that we have and we want a victory.
"We know the importance of the game and the significance of El Clasico and we will go there to win."
Barca will definitely be without captain Carles Puyol after he suffered a dislocated elbow in midweek while his centre-back partner Gerard Pique has not played in a fortnight because of a foot injury.
Mourinho, meanwhile, should be able to select near enough his strongest team, with Kaka pushing for a starting berth after some impressive recent displays.