Champions Real, who are fifth after a poor start to the campaign, trail leaders Barca by eight points but there is little doubting that come next May the world's two richest clubs by revenue will be the only ones battling for the title.
Ten years ago, Galician sides Depor and Celta were both up there competing for the top spot and finished third and fourth respectively. Vicente del Bosque's Real team took the 2002-03 league title, with Barca finishing sixth.
That season, Depor triumphed 2-0 over Barca in the corresponding fixture at the Riazor, just a few months after beating Real 2-1 to win the King's Cup final the previous season. Celta held Real 1-1 at the Bernabeu.
A repeat of those results this time round would be considered major upsets.
While Barca and Real have steadily increased their earnings up to the 500 million euro mark over the last decade, Celta and 2000 champions Depor have both crumpled under crippling debts.
Depor, with a budget of around 40 million euros ($52.48 million) and a debt of over 100 million, are in a precarious position having just returned from a season in the second division.
After an opening day win, their coach Jose Luis Oltra is under pressure following a run of three draws and three defeats which has left them 18th in the standings.
Celta, operating on a budget of around 33 million euros, are in a slightly healthier position.
Relegation in 2007 led to the club going into administration with a debt of around 70 million euros but their return after five years out of the top flight has started a little better.
Under coach Paco Herrera, a former assistant to Rafa Benitez at Liverpool, they have taken nine points from seven games and lie 12th.
Celta midfielder Borja Oubina was a member of the side that won on their last two trips to the Bernabeu in the 2005-6 and 2006-7 seasons before they were relegated.
"The budgets of the two big teams are much larger now and it is tougher to beat them," the 30-year-old told sports daily AS.
"But we have nothing to lose and this could work in our favour."
Jose Mourinho's Real appear to have suffered the most from the break for internationals going into Saturday's game (1600 GMT).
Brazil defender Marcelo has been ruled out for three months with a fractured bone in his foot, while fellow full backs Fabio Coentrao and Alvaro Arbeloa also returned with muscle injuries.
Karim Benzema, Gonzalo Higuian and Sami Khedira are all carrying knocks.
Unbeaten Barca visit Depor later on Saturday (2000) when any dropped points could see second-placed Atletico Madrid climb to the summit when they visit Real Sociedad on Sunday (1930).
Diego Simeone's side, La Liga's only other unbeaten team, are kept off the top by goal difference from Barca.