This season the Galician side’s Riazor stadium has proven an unhappy hunting ground for top clubs.
Atletico Madrid, Villarreal and Valencia have all been held to draws there, while Barcelona succumbed to a shock 2-1 defeat last month as the battle by Pepe Mel’s side to avoid the drop gathered pace.
After losing a dramatic Clasico 3-2 to Barca on Sunday with the last kick of the game – a result that sees the Catalans move ahead at the top of the table because of their superior head-to-head record - Madrid know they cannot afford defeat as they bid to lift their first La Liga title for five years.
Coach Zinedine Zidane insisted that, while they might currently sit second, the fact that Madrid have played one game fewer means they still control their own destiny. "Nothing changes, we still have things in our own hands and we are only thinking about Wednesday’s game," Zidane said.
"It (the Clasico) was not about deciding who wins La Liga. A win, loss or draw means that nothing changes. We are disappointed as overall we did not deserve to lose, but football is like that. We do not have too much time to wallow and have to get over it."
Real will be without captain Sergio Ramos for the trip after he was sent off against Barcelona and have Nacho as their only recognised senior centre-back, with Pepe and Raphael Varane out injured.
Depor striker Florian Andone will be looking to capitalise on Ramos's absence.
"It's a relief he's not playing. He's the best centre-back in the world," he said. "It would’ve been better if they had beaten Barca, but that doesn't matter to us. They’re a great side and it doesn't matter who lines up for them. They’ve got enormous strength. But we beat Barcelona and why can't we do the same to Madrid?"
Barca, meanwhile, host bottom of the table Osasuna and will be ready to pounce should Madrid drop points in what has been a topsy-turvy campaign.
"This is a season that weighs like five. So many things have happened, both good and not so good, things I’ve already forgotten," coach Luis Enrique said.
"We're top of the table now but Madrid have a game in hand. It will be tight and go right down to the wire."
Neymar will serve the final game of his three-match suspension against Osasuna, who could be relegated if they lose and results in other games go against them.
Elsewhere, Sevilla host Europa League semi-finalists Celta on Thursday as they aim to consolidate a place in the top four, while King’s Cup finalists Alaves host Eibar in a Basque Country derby.
(Editing by Gareth Jones)
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