Second-placed Real visit the side three points below them in the standings and local media have made much of the Portugal forward's irresponsible behaviour in collecting two yellow cards last weekend to earn a suspension for the Valencia game.
The first was for taking his shirt off to celebrate scoring a goal and the second, picked up minutes later, was for kicking an opponent.
Coach Manuel Pellegrini was left without his most potent forward and playmaker Kaka, who is nursing a groin problem.
But Valencia stalwart David Albelda was quick to draw attention to the absence of Spain midfielder Silva.
"If Ronaldo and Kaka don't come that's great for us, and if someone else is out as well even better," Albelda told a news conference ahead of Saturday's game.
"We're without Silva but we don't keep going on about it. Silva is as good as they are and plays in a similar position."
The absence of Ronaldo and Kaka comes with Real needing to prove they can win the big games. In La Liga they have lost away to leaders Barcelona and fourth-placed Sevilla.
The match also gives third-placed Valencia the chance to close in on the top two. They are unbeaten in 15 matches in all competitions.
BARCELONA DERBY
Both Real and Valencia will be hoping Espanyol can rise to the occasion for the Barcelona derby, when they visit the Nou Camp on Saturday.
The unbeaten champions have a five-point lead at the top, having played a game more than their rivals, and are in a rich vein of form.
Espanyol, 14th, have lost four on the trot without scoring a goal, but were in a similarly sticky situation when they travelled to face Barca last year as the bottom-placed club.
Their aggressive, physical approach disrupted the eventual treble-winners and they stole a shock 2-1 victory.
This year, however, they come into the game after consecutive 4-0 defeats.
"Last week I felt humiliated and I want to transmit this to the players so that they react. I want them to feel the same anger," Espanyol coach Mauricio Pochettino said.
Barca have a doubt over Lionel Messi who twisted an ankle away to Dynamo Kiev in the Champions League on Wednesday.
Fourth-placed Sevilla will be looking to get back on track after successive draws when they visit Sporting Gijon on Sunday, while Atletico Madrid host Villarreal.
