Real Madrid travel to the Ramon Sanchez Pizjuan looking for the win that will keep them top of the table before they face Barcelona at the Santiago Bernabeu in a fortnight.
It's a fixture that has generally favoured Los Blancos although the Andalusians have still managed to win nine games against Real in the last decade.
Although Real have the lion's share of victories that's still a win ratio that's not to be sniffed at and Unai Emery will want his troops to bounce back from the disappointment of a humbling defeat against Manchester City in the midweek Champions League fixture.
Let's take a look at three things that could affect the outcome of this one...
There have been at least two goals scored in every match bar four out of the last 26 fixtures between these sides.
Both like to attack at every opportunity and the setup of both teams has always been conducive to a high-scoring game.
In the last four years, Real have hit Sevilla for six twice and for seven on a single occasion. Rafa Benitez will be delighted if his side can keep up that kind of attacking excellence.
Although Karim Benzema will still be missing, the return of James Rodriguez will see a decent injection of pace and skill down the left side which could cause the hosts problems.
Emery finally got the monkey of a victory over Barcelona off of his back earlier in the campaign. He'd like nothing better than another home victory over one of La Liga's "big boys."
Keylor Navas has performed unbelievably well in games this season and there has been some truth behind claims that he has been responsible for keeping Real at the top of the table.
Even when the outfield players have been below par, the Costa Rican stopper has been at his very best.
When you consider that he could've been plying his trade in the red half of Manchester and cried when the move didn't come off, it makes his professionalism in the role even more noteworthy.
Unfortunately for both player and club, Navas is injured and will sit this one out.
Kiko Casilla's lack of minutes since his transfer from Espanyol won't have escaped Emery and it wouldn't be a surprise if tried to bombard the substitute keeper with some testing high balls, especially in the opening exchanges.
No stopping Ronaldo
If there's one player who seems to always write his name all over this fixture it's Cristiano Ronaldo.
Sevilla is one team that he loves to play against and the Portuguese has scored 11 of the last 16 Real Madrid goals at the Ramon Sanchez Pizjuan.
In his last four games against the Andalusians he has 10 goals. Three hat-tricks and a solitary strike.
It doesn't really get much better than that and it goes without saying that Sevilla will have to give Ronaldo some extra special attention if they want to stop him this time.