Barca suffered a painful 3-1 home defeat to Jose Mourinho's side on Tuesday as they were dumped out 4-2 on aggregate in the semi-finals of the Copa del Rey.
That defeat, allied to the Champions League loss against AC Milan, has led to suggestions from some in the Spanish media that teams have figured out how to counter Barcelona and minimise the threat of Lionel Messi, who is expected to feature this weekend despite feeling unwell earlier this week.
Barca hold a dominant 12-point lead over second-placed Atletico Madrid in the title race, with Real a further four points adrift, and the Catalan side have followed each of their five defeats this season with a victory.
But they will be keen to prove they have not been unduly affected by the absence of coach Tito Vilanova, who is currently in New York receiving treatment after having a second lump removed from his parotid gland last month.
Madrid may be effectively out of the race to secure the La Liga title, but their victory is a timely boost for Mourinho, who has come under severe pressure.
And midfielder Xabi Alonso has heaped praise on the Portuguese ahead of Saturday afternoon's clash.
Speaking to UEFA's Champions Matchday magazine, the Spain international said: "Above all I am struck by his ability to empathise with and reach his players, which is a hard thing to do. When you see a group in front of you that support you, believe in the ideas you are transmitting... that's what a leader does. And our coach is a leader like that. For me, he is one of the best coaches.
"Apart from his knowledge of the game, he masters many elements in terms of tactical variations within each match."
Elsewhere, Atletico, boosted by their own passage to the Copa del Rey final by seeing off Sevilla, will look to try to take advantage of any slip-ups from Barca when they travel to face Malaga on Sunday.
Coach Diego Simeone told a press conference: "For us it is the wrong time to talk about the final, although we are glad people will be going to work happy. But we now have to focus on our game against Malaga."
Sevilla will look to recover from their cup disappointment when they face struggling Celta Vigo, while bottom club Deportivo La Coruna desperately need a win at home to Rayo Vallecano if they are to boost their fast-fading survival hopes.
Valencia and Real Sociedad are snapping at Malaga's heels as the chase for the fourth and final Champions League spot hots up, and they will be looking to pick up victories against Levante and Real Betis respectively.
Relegation-threatened Real Mallorca travel to Granada, while Real Zaragoza - who lie just two points above the drop zone - meet mid-table Getafe.
Real Valladolid will travel to Espanyol and Osasuna host Athletic Bilbao.