Barcelona play Granada on Sunday, allowing Los Blancos the opportunity of taking the lead in the top flight, if only temporarily.
Real are fresh from their 2020 Spanish Super Cup victory after defeating Atletico Madrid on penalties following a goalless draw in Saudi Arabia last weekend.
Sevilla have been largely consistent this season and sit fourth in the division.
Date: Saturday, January 18
Time: 4 p.m. local, 3 p.m. GMT, 10 a.m ET
TV: BeIN Sports (USA)
Odds: Madrid: 61-100, Sevilla: 41-10, draw: 67-20 (via Caesars)
Los Nervionenses arrive at the Santiago Bernabeu Stadium as underdogs, and a dip in form has been ill-timed ahead of their trip to the capital.
Despite just one win in five in all competitions, their La Liga record continues to impress, with only one defeat in their last 11 league matches.
According to AS, Sevilla will give Madrid a guard of honour after their Super Cup victory, but all eyes will be on manager Julen Lopetegui as he returns to his former club.
Lopetegui was dismissed as Spain coach just before the 2018 FIFA World Cup after it was announced he would join Real at the end of the tournament, but the former Porto boss lasted 138 days before he was sacked by Florentino Perez.
The 53-year-old failed to get to grips with the challenge at the Bernabeu, and a 5-1 defeat at Barca was the final straw.
Lopetegui took the reins at Sevilla last June, and his team have proved to be an uncompromising defensive unit, conceding only 18 goals in their 19 league outings.
However, a trip to Real is always a difficult prospect, especially when Zinedine Zidane has his players singing from the same hymn sheet.
Perez will be delighted with how his club have responded after a difficult 12-month period. Zidane began his second spell in charge in March 2019, and the post-Cristiano Ronaldo era has been tough.
However, Real are title challengers once again after finishing 19 points behind champions Barca last term. Los Blancos lost 12 of their 38 league games across the season and ended third—an unacceptable performance for the Spanish giants.
Karim Benzema has proved to be reliable in Zidane's attack, with big-money signing Eden Hazard out due to a microfracture in his ankle.
The Frenchman has returned excellent figures of 16 goals and seven assists in La Liga and Europe this season, and he's helped keep his team in the hunt for trophies.
The player missed the Super Cup success due to a bruised leg, but he could be available against Sevilla after returning to training, according to Amitai Winehouse for MailOnline. Gareth Bale could also return after illness, bolstering Zidane's options.
Real's Super Cup final win was their 16th game without defeat, but they will be wary of Sevilla's ability to earn results ahead of Saturday's intriguing clash.