This fixture had to be postponed earlier in the season, due to Madrid's involvement in the Club World Cup, but Wednesday's meeting gives Carlo Ancelotti's men the opportunity to cement their place at the top of the table.
The Champions League holders come into the game in high spirits, having beaten Real Sociedad 4-1 at home at the weekend to record a fourth consecutive league success.
Ancelotti hailed the performance of Karim Benzema after the Frenchman netted twice on Saturday and the coach will hope for a repeat performance as his team continue to manage without star man Cristiano Ronaldo, who serves the second game of his two-match suspension.
Following the win over Sociedad, Ancelotti suggested that he could make alterations to his team as he looks to manage the players' levels of fatigue.
"We have to assess the exertion we've put in in this game," he said.
"We know that we have a very important game to try to increase our lead. I might change something because we need a fresh team."
Aside from Ronaldo's enforced absence, Ancelotti looks likely to still be without Luka Modric (thigh), while defender Pepe remains a doubt with a rib injury.
Sevilla, meanwhile, are in strong form themselves and have only lost one of their past eight top-flight outings.
Iago Aspas' late winner earned them a 3-2 success over Espanyol on Sunday, a result that further enhanced their hopes of securing a top-four finish and a return to UEFA Champions League football.
Sevilla saw goalkeeper Beto substituted at half-time due to injury and it remains to be seen whether he will recover in time, with Sergio Rico poised to step in.
Following Sunday's victory, Emery began to turn his attention to facing Real, as he rejected any suggestion his side would be happy to take a draw.
"We play to win, not just to offer a good image of ourselves, but naturally by playing well, we'll have more options of winning," he said.
"We'll try to recover as many of our players as we can, so that those who play on Wednesday can give it all their energy."
Although this is the first league meeting between the two sides this season, Real have already beaten Sevilla 2-0 in the UEFA Super Cup back in August, while the visitors will have torrid memories of a 7-3 thrashing in the corresponding fixture in 2013-14.
