Both clubs have a track record of rising to the occasion and will be out to test the staying power of the top two who had demanding road trips in the Champions League during the week.
Real beat BATE Borisov 1-0 in a freezing Minsk on Tuesday to qualify for the last 16, but have found Getafe's Coliseum an equally inhospitable venue despite being just down the road.
They notched up their first win at Getafe with a 1-0 victory last season and have beaten their modest neighbours only three times in a total of eight league encounters.
Getafe's new coach Victor Munoz has so far struggled to reach the standards set under Michael Laudrup last season, when the side reached their second consecutive King's Cup final and the quarter-finals of the UEFA Cup. They lie 14th.
Last weekend, however, they reverted to type, tripping up Barcelona at the Nou Camp and ending the leaders' nine-match winning streak with an intelligent tactical display to draw 1-1.
"The draw in Barcelona has given us a lot of confidence for Saturday's game," Getafe striker Manu del Moral said.
"Real arrive wounded, with a lot of injuries, and it seems not playing very well. But they are who they are and have players who can turn a game in a moment."
Media talk of a crisis at the Bernabeu due to a spate of injuries and their exit from the King's Cup look premature with the side now second in the standings, though their recent performances have not been convincing.
STUBBORN OPPONENTS
Sevilla, who are fifth, have been similarly stubborn opponents for Barcelona and have relinquished all three points only once in the last four meetings at the Sanchez Pizjuan.
Barca secured top spot in their Champions League group with a 5-2 victory away to Sporting Lisbon on Wednesday.
Lionel Messi, who was rested as a precaution because of an injury for the draw against Getafe, started and proved how important he is to the side by steering them into a 3-0 lead before being taken off in the 57th minute.
"I am in good shape and felt fine today. A few days ago I had a scare but luckily that's all it was," Messi said afterwards.
Third-placed Villarreal visit bottom club Recreativo Huelva on Sunday when fourth-placed Valencia host in-form Real Betis.
Atletico Madrid, in sixth, will be able to celebrate qualifying for the knockout stage of the Champions League with their fans when the doors of the Calderon open again for the visit of Racing Santander after they beat PSV Eindhoven in an empty stadium as a punishment for crowd trouble.
