Both sides will be looking to get a positive result to put them in good stead to book a place in the semifinal.
Considering the sides' pedigree and the quality of players available to both managers, Real Madrid and Liverpool's clash is arguably the most high-profile. Fans have naturally turned their attention to predicting the likely winner in the lead-up to the clash.
One man who has weighed his thoughts on the fixture is Xabi Alonso. The World Cup winner has identified five key battles that could determine the outcome of the game.
He highlighted the battles of Raphael Varane vs. Mohamed Salah, Luka Modric vs. Thiago Alcantara, Ferland Mendy vs. Sadio Mane, Toni Kroos vs. Fabinho and Karim Benzema vs. Ozan Kabak as being key to the outcome of the tie.
Each of the players listed have key roles to play for their respective teams and one triumphing over the other could be the difference between defeat and victory.
Xabi Alonso is one of a handful of players to represent both Real Madrid and Liverpool with distinction.
He shot to fame following his five-year spell at Anfield between 2004 and 2009, where he played a key role in helping the Reds triumph in the 2005 UEFA Champions League final.
Alonso departed Anfield for Real Madrid in 2009 and spent another five years in the Spanish capital. The Spaniard won the UEFA Champions League in his final game with Real before joining Bayern Munich.
Alonso was also an integral member of the all-conquering Spain sides. He was an ever-present player as the Spanish national team won a World Cup in between consecutive European Championships.
Alonso has since ventured into football management following his retirement and is currently the Real Sociedad B team manager.
Real Madrid and Liverpool head into marquee fixture in confident mood
Real Madrid and Liverpool's domestic campaigns have been inconsistent to date, but both sides have seen an upswing in results in recent games.
The Reds were 3-0 victors over Arsenal away from home, while Real Madrid defeated Eibar courtesy of goals from Karim Benzema and Marco Asensio.
This will put the two sides in a buoyant mood heading into this game, and the UEFA Champions League might represent both teams' best shot at winning a trophy this season.