Louis van Gaal, Jurgen Klopp
A fired up Jurgen Klopp, right, will face off with Manchester United manager Louis van Gaal in the Europa League last 16. Getty Images

They are the two most successful clubs in the history of English football, winning 38 titles between them, and they are also England’s two most successful continental exports, landing a combined eight European Cups. The rivalry between Liverpool and Manchester United, though, has never before graced the European stage. Until Thursday, that is.

It may not be the Champions League, but the Europa League Round-of-16 meeting between the two sides from England’s North West will still have plenty riding on it.

“Games like this are the mother of all football games and that's what you want,” Liverpool manager Jurgen Klopp said ahead of the matchup at Anfield. “We all love football. In each and every region of the world you have games like this. Maybe not with as big names.

“Liverpool v United is one of the best I can imagine. For me to be a part of it I still can't get enough. It's the best thing imaginable.”

Klopp has insisted from the moment the tie was announced that it is one he is relishing, with it adding spice to a competition that has not always been treated with the utmost importance by English clubs over the years. With both clubs struggling in the Premier League this season, however, the Europa League carries plenty of significance.

For both, winning the competition presents perhaps their best opportunity to qualify for next season’s Champions League. Liverpool currently sit seventh in the Premier League, six points off the top four, while Manchester United are one place and three points better off, although having played a game more.

“You have to win—there is no difference [between a league and a cup game],” Manchester United manager Louis van Gaal said. “United and Liverpool is always a big game. It's historical and even bigger now because both teams are fighting for a Champions League place.

“I noticed that you [the English media] have a negative view [of the UEFA Europa League] but against teams like Midtjylland there were how many fans? 58,000. The fans of Manchester United are appreciating it. How many fans do I think we'll have against Liverpool? Maybe 75,000. I think Anfield is also sold out, so that's what I have to say—it's very important for both teams and the fans want to see the duel between us.”

Manchester United required a second-leg fight back to overcome Danish champions Midtjylland in the last round, winning 5-1 at Old Trafford after going down 2-1 in the first match. That victory came as part of a resurgent run of form for United as the pressure on Van Gaal was eased by a four successive victories. But that revival was tempered on Sunday by a 1-0 loss to West Brom.

Liverpool, meanwhile, have now gone four matches unbeaten in the Premier League as they show signs of finding some consistency for the first time since Klopp took over last October. There were plenty of nerves, though, in sealing their place in the Europa League last 16 after a 1-0 win over Augsburg at Anfield sent them through by the same scoreline on aggregate.

Ahead of Thursday’s Round of 16 first leg, Klopp has a significant fitness concern after midfielder James Milner missed training on Wednesday due to a virus. If he does miss out, he would join Lucas Leiva, Joe Allen, Joe Gomez and Danny Ings on the sidelines.

Manchester United have received a boost, with Antonio Valencia fit to return to the squad, although Wayne Rooney, Ashley Young, Luke Shaw, Phil Jones and Cameron Borthwick-Jackson remain sidelined. Adding to the list of absentees, Jesse Lingard is suspended, while Bastian Schweinsteiger has only just returned to training and is unlikely to feature.

Probable lineups

Liverpool
G: Mignolet

D: Clyne, Lovren, Sakho, Moreno

M: Henderson, Can

Lallana, Firmino, Coutinho

F: Sturridge

Manchester United
G: De Gea

D: Darmian, Smalling, Blind, Rojo

M: Schneiderlin, Herrera

Martial, Mata, Memphis

F: Rashford

Kickoff Time: 3:05 p.m. EST

TV Channel: Fox Sports 2

Live Online Stream: Fox Sports Go, Fox Soccer 2Go, ESPN3