Jose Mourinho's men are midway through their Champions League quarter-final with Tottenham Hotspur, though they travel to London on Wednesday with a handsome 4-0 advantage, and they welcome the La Liga leaders to the Bernabeu next Saturday.
Four days later the two teams meet again in the King's Cup final, and the likelihood of a Champions League semi-final clash between the Spanish giants drew closer when Pep Guardiola's side routed Shakhtar Donetsk 5-1 in the first leg.
Keeping his players fresh and injury-free for those matches while trying to keep alive their fading league title hopes will be Mourinho's priority in Bilbao.
"It's for moments like these that they have spent so much money on their squad," Bilbao coach Joaquin Caparros, who guided his side to a 1-0 win in the same fixture last season, told sports daily Marca.
"Now is the time for squads... and Madrid have a magnificent one. I'm sure they will put out a starting XI full of internationals.
"History shows that until it is mathematically impossible Madrid will not give up the league as lost."
Barca's push towards a third consecutive La Liga crown was helped by Real's shock home defeat by lowly Sporting Gijon last weekend, and that should serve as a reminder when they host basement side Almeria on Saturday.
