#3 Joao Felix (Atletico Madrid) vs Raphael Varane/Nacho (Real Madrid)
After a blistering start to the season, Atletico Madrid sensation Joao Felix has lost his way in recent months, but he will be raring to go against Real Madrid.
The Portugal international stepped off the bench to score a spectacular goal against Villarreal last week; his celebration was very much a statement of intent that he is yearning to make a mark in the big games.
Felix's best position comes as a decoy to the main striker, and he seems to have struck an excellent understanding with Luis Suarez.
Meanwhile, in the absence of Sergio Ramos, Raphael Varane has become the de-facto leader of the Real Madrid defence. The Frenchman, alongside Nacho, will have to keep a keen eye on Joao Felix, though.
The former Benfica man is at his best with the ball at his feet, with his trickery, close control and excellent technique, helping him draw defenders while his teammates are free to exploit spaces left behind.
#2 Zinedine Zidane (Real Madrid) vs Diego Simeone (Atletico Madrid)
It is not only on the field that key battles will take place. Arguably the most important battle will see two of the best managers in the world, Zinedine Zidane and Diego Simeone, try to tactically outwit the other from the touchlines.
Both men have shown a penchant for preferring substance over style. And their respective teams' compact style of play means not too many fireworks could be expected.
Zidane is the more short-staffed of the two, as several key Real Madrid players are currently sidelined because of injury. The Frenchman will have to make do with what he has available, although Rodrygo and Lucas Vazquez could return against Atletico Madrid.
Diego Simeone has watched Atletico Madrid's previously comfortable lead at the summit get whittled down in recent weeks. He will be keen on getting a first competitive victory over Real Madrid in three years to consolidate his team's place at the La Liga summit.
#1 Luis Suarez (Atletico Madrid) vs Thibaut Courtois (Real Madrid)
Luis Suarez has been the driving force behind Atletico Madrid's title charge this season, making a mockery of those who suggested that his time at the highest level was over.
In hindsight, Barcelona's decision to let Suarez join a direct rival looks rather foolish, as his 16 league goals are second only to Lionel Messi in this season's La Liga goal-scoring charts.
However, after hitting a dry patch in recent weeks, Luis Suarez will be looking to get back among the goals. So the game against Real Madrid could offer him an excellent opportunity to do so.
The Uruguay international is no stranger to Los Blancos, having taken part in El Clasico for six years. Suarez has a rather impressive record of 11 goals and five assists in 17 games against Real Madrid, and he has the ability to effectively end their title charge this season.
However, in the opposition goal will be Thibaut Courtois, who could have other ideas after enjoying a breakthrough campaign at Real Madrid last season.
Last season, the 28-year-old won a second Zamora trophy, bringing an end to Jan Oblak's three-peat. Courtois has continued his fine run of form between the sticks this term as well.
With Real Madrid struggling for goals and missing several key defenders, Courtois has taken on an even bigger role and could have a big role to play against league leaders Atletico Madrid on Sunday.