The Reds currently top the table under the new-look UEFA format but historically have struggled against defending champions Real.
Liverpool are winless in their last eight meetings, losing seven, including two Champions League finals during Jurgen Klopp's era.
However, the Merseysiders have cause for optimism this time as the only team with a perfect record this season under Arne Slot.
Liverpool have won all four of their European matches following a 4-0 win over Xabi Alonso's Bundesliga kings Bayer Leverkusen.
In contrast, 15-time Champions League winners Madrid have been a shadow of their former selves so far, having already lost twice.
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Liverpool vs Real Madrid: Ballon Bore
Vinicius Junior hit out at UEFA for football's packed schedule after his latest injury has ruled him out of the trip to Anfield.
"The crazy calendar... Time to recover!" the Ballon d'Or runner-up wrote on X on Monday evening.
The 24-year-old's absence will come as a boost to Liverpool, such is his extraordinary record against the Premier League side.
Vinicius is unbeaten in his five games facing the Reds, winning four times while the other was a goalless draw at Anfield in 2021.
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His most recent trip to Liverpool's home stadium saw him mastermind Madrid's comeback from two goals down to win 5-2.
That accounted for two of his five overall against Slot's side, with another being the match-winner in the 2022 Champions League final.
Liverpool won their first three games against Real Madrid in European competition (between 1981 and 2009), however, they're winless in their eight meetings since then, suffering seven defeats (D1).
Real Madrid are the team that Liverpool have lost most often against in European competition (7). Indeed, among sides they've faced 5+ times in Europe, they're also the opponent they have lost the highest percentage of their games against (64% - seven losses in 11 games).
Liverpool are the only team with a 100% record in the UEFA Champions League this season, winning all four games. The only previous time they've won their first five matches in a major European campaign was in 2021-22 (won first seven).
Liverpool vs Real Madrid: Team news
Both teams are battling mounting injury issues, with none of Alisson Becker, Kostas Tsimikas, Diogo Jota or Federico Chiesa expected to play.
Trent Alexander-Arnold faces a late fitness test to return against the club he's linked with joining next summer but is also a major doubt.
Madrid will travel with only 19 players - which includes three goalkeepers - with Vini Jr the headline absentee.
Dani Carvajal, David Alaba, Rodrygo, Aurelien Tchouameni and Eder Militao are all out, but Lucas Vazquez has a chance of featuring.
Real Madrid forward Kylian Mbappé has scored 49 goals in 77 appearances in the UEFA Champions League. If he finds the net in this game, he'll be the fourth-quickest player to 50 goals in the competition (78th appearance), behind Ruud van Nistelrooy (62), Lionel Messi (66) and Robert Lewandowski (77).
Since the start of last season (and as of the end of MD4), the three midfielders/forwards who've created the most chances from open play in the UEFA Champions League are all current Real Madrid players: Jude Bellingham (32), Vinícius Júnior (31) and Kylian Mbappé (31).
Ryan Gravenberch has recovered possession 30 times in the UEFA Champions League this season; the most by any central midfielder in the opening four matchdays. Meanwhile, the Dutchman has completed 93% of his passes in the competition this term; the highest of any Liverpool player (min. 50 pass attempts).
Liverpool vs Real Madrid: What has been said?
Jamie Carragher claimed he is 'very disappointed' in Mohamed Salah's decision to issue his contract update on the eve of this huge game.
After he scored two goals in Liverpool's 3-2 win at Southampton on Sunday, Salah said he's not received any offers from the club to stay.
He also claimed he's 'probably more out than in', and his comments have not sat well with fellow club legend Carragher, who called him 'selfish'.
Speaking on Monday Night Football for Sky Sports, he said: "I must say, I am very disappointed with Mo Salah."
When asked to explain his reasoning, Carragher explained: "That interview yesterday, last night after the game and it comes out today.
"Liverpool have got Real Madrid midweek and they've got Manchester City at the weekend, that's the story for Liverpool right now.
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"Mo Salah, we're all quite aware, certainly the local reporters are in Liverpool, that in the seven years he's been at the football club, he's stopped in the mixed zone twice, which is his right, which is absolutely fine.
"But he decided to stop for the third time away at Southampton on the back of winning Liverpool the game and putting that out.
"Now, the most important thing for Liverpool Football Club this season is not the future of Mo Salah, it's not the future of Virgil van Dijk and it's not the future of Trent Alexander-Arnold.
"The most important thing is Liverpool winning the Premier League, that is more important than any of those players.
"And if he continues to put comments out or his agent keeps putting cryptic tweets out, that's selfish, that's thinking about themselves and not the football club."
Half of Liverpool's goals in the UEFA Champions League this season have been scored following crosses (5/10), with their five such goals being the most of any side. Each of their last three goals from crosses in the competition have been assisted by Mohamed Salah (one v Bologna and two v Bayer Leverkusen).
Real Madrid have only been ahead on the scoreboard for 12% of their total match time in the UEFA Champions League this season (47 minutes and 10 seconds overall). Meanwhile, Liverpool have been ahead for 64% of their minutes played in the competition this term; the highest percentage of any team across the opening four matchday.
Real Madrid have lost two of their last three UEFA Champions League matches (W1), as many as they had in their previous 28 games combined (W20 D6). They have never lost three games in a single group phase in a season before.
Liverpool vs Real Madrid: How to follow
This Champions League clash is set to take place on Wednesday, November 27.
Kick-off at Anfield is scheduled for 8pm.
talkSPORT will have live coverage from Merseyside, with Adrian Durham serving as your presenter.
Commentary will come from Jim Proudfoot and former England captain Stuart Pearce.
talkSPORT.com will also have updates in our dedicated live Champions League blog.
To tune in to talkSPORT through the website, click HERE for the live stream.
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