The champions were on the end of a 7-2 humiliation in the reverse fixture at Villa Park in October - one of nine defeats they have suffered this season to leave them playing catch-up in the top-four race.
A huge amount has transpired since these two last faced off in the league more than six months ago, but Liverpool will no doubt feel as though they have some unfinished business after finding themselves on the wrong end of one of the most remarkable Premier League scorelines of all time.
The champions had made a strong start to their title defence heading into that fateful day at Villa Park, boasting a 100% record of three wins from three, including dominant back-to-back victories over Chelsea and Arsenal.
In hindsight, what followed was the first real glimpse of what would become a torrid attempt to retain the title this season, and even before their defence had been ravaged by injury, they found themselves ripped apart by Villa.
Ollie Watkins bagged a hat-trick, Jack Grealish scored twice and John McGinn and Ross Barkley both got in on the act as well as Liverpool were humbled, humiliated and hammered by a team that struggled against relegation last season.
Jurgen Klopp usually insists that each game is a new game and that past meetings will have no bearing on future showdowns between certain sides, but even he might be tempted to tap into the bruised egos Liverpool suffered in October ahead of Saturday's match.
These two sides have faced off once since then, with Liverpool surviving a scare against a youthful Villa team in the FA Cup third round in January, but it is the last Premier League meeting which will dominate the buildup to this game.
Villa will not be expecting a repeat, although they have every reason to be confident of a first Premier League double over Liverpool since the competition's inaugural season in 1992-93.
Indeed, even before this match only Man City in 2017-18 have ever scored more goals against Liverpool in a single Premier League season, with Villa needing two goals to become outright holders of that small slice of history.
It is even more difficult to know what to expect from Liverpool now than it was ahead of the first meeting between the two sides this season, with a U-turn in home form hampering their top-four hopes so far in 2021.
Incredibly, each of Liverpool's last six Premier League wins have come away from home - only the second time they have been on such a run in their history after February to August 1955 - while their last six Premier League outings at Anfield have ended in defeat.
Huddersfield Town were the last team to lose seven top-flight home games in a row on their way to relegation in February 2019, and Liverpool's tally of six this season is already their most in a campaign since 1953-54, when they finished bottom of the table.
Just as concerning as their losing run will be their lack of goals on home turf, having netted just once in those six defeats and, excluding penalties and own goals, failed to score with any of their last 115 shots at Anfield.
It has been more than a month now since their last Premier League game at home, though, and Klopp will be hopeful that such a gap is enough to break whatever bizarre hoodoo has befallen his side since the turn of the year.
The highest any team has ever finished in the top flight having lost six or more consecutive home games in a season is ninth - a dubious feat achieved by Sunderland in 1946-47 - making the prospect of securing a top-four finish all the more unlikely should that run continue any longer.
A good weekend last weekend means that Champions League football next season is still very much within reach, though, and due to the schedule of games this weekend Liverpool would actually climb into the top four temporarily at least with a win over Aston Villa.
The importance of securing a place in the top four has grown even more in the wake of Liverpool's 3-1 defeat at the hands of Real Madrid in their Champions League quarter-final first leg on Tuesday night, when the Reds were punished for an error-strewn first-half display in particular.
After such a dominant 3-0 win over Arsenal last weekend, the Madrid performance was proof that Liverpool are by no means back to their very best just yet, but Klopp will be hopeful that things do now improve domestically at least.
The reverse fixture and Liverpool's home league form are enough to make Villa fancy their chances this weekend, though, and Manchester United and Chelsea are the only visiting teams to have won more Premier League games at Anfield in the Premier League era.
Villa have only won one of their last 27 top-flight away games against the reigning champions, and have not done the double over the champions since 1989-90, but Liverpool have now been mathematically dethroned and Villa head into the match off the back of a victory.
Villa have not won back-to-back matches since Boxing Day, though, and inconsistency has prevented them from really pushing for a top-four finish in a season when many dark horses have fancied their chances.
Even so, 2020-21 is sure to go down as a success; they are 18 points and 10 places better off than at the same stage of last season, and well on course for their first top-half finish in a decade.
Indeed, victory at Anfield would leave them only two points behind the champions with a game in hand, keeping alive their hopes of sneaking a Europa League spot in the process.
No team has kept more away clean sheets than Villa's eight in the Premier League this season, and another on Merseyside this weekend would set a new club record for that particular metric in the top flight.
Smith's side could be one of the worst opponents possible for a Liverpool team struggling so much in front of goal at home, then, making this showdown every bit as intriguing as the unforgettable reverse fixture.
Klopp has confirmed that Naby Keita's first-half withdrawal against Real Madrid in midweek was for tactical reasons, meaning that the midfielder is available to feature again this weekend.
The Liverpool boss is likely to have one eye on Wednesday's return fixture against Los Blancos, although he will know that Saturday's match could be every bit as important to their hopes of being in the Champions League again next season.
That said, Mane's record against Villa - eight goals in seven appearance across all competitions - could be enough to see him start once again.
Villa will still be without captain Grealish, who has missed the last seven games with a shin injury and now looks set to be sidelined until May after suffering a setback in his recovery. Wesley is Smith's only other injury worry.
Barkley will hope to earn a recall to the starting XI for this one, while Trezeguet's brace off the bench last weekend should be enough to see him included.
Liverpool possible starting lineup:
Alisson; Alexander-Arnold, Phillips, Kabak, Robertson; Milner, Fabinho, Jones; Shaqiri, Firmino, Mane
Aston Villa possible starting lineup:
Martinez; Cash, Konsa, Mings, Targett; Luiz, McGinn; Traore, Barkley, Trezeguet; Watkins
We say: Liverpool 2-1 Aston Villa
The reverse fixture proved that anything can happen in this fixture, and Liverpool's home form coupled with Villa's away record this season suggests that this could be another difficult contest for Liverpool.
However, the prospect of breaking into the top four with a win should be enough to spark Liverpool back into form at Anfield, and their imperious performance against Arsenal last weekend hints that they could be getting back into their stride domestically at least.
Watch the Sports Mole Football Shorts prediction for this game below:
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