Fresh from dishing out Atalanta's heaviest ever home European defeat on matchday three, Liverpool sit comfortably at the top of Group D, five points clear of their closest challengers.
The trip to Bergamo in the reverse edition of this fixture had all the hallmarks of a difficult match for an injury-depleted Liverpool squad, yet their 5-0 victory was an emphatic statement of intent.
The six-time European champions are again among the favourites to go all the way this season, despite the fact that their injury problems have grown significantly worse since that win in Italy on November 3.
The prospect of sealing European qualification with two games to spare - and the ability to rotate more as a result of that - will be a particularly appealing one for a squad which has been stretched to the limit, missing 10 first-team players and more than half of their first-choice XI for Sunday's home Premier League match against Leicester City.
Not that that seemed to affect them; Jurgen Klopp's side were dominant from start to finish of their 3-0 triumph over a Leicester side that went into the weekend top of the table, and that was a scoreline which flattered the Foxes more than it did Liverpool.
The Reds now sit joint-top of the Premier League table, and the manner of the result and performance against Leicester will have set some minds at ease that Liverpool can still be a force both domestically and in Europe despite their injury problems.
Liverpool have won all three of their group games so far and, just as crucially considering their defensive record in the Premier League, they have kept clean sheets in all three of those wins too - the only club to boast a perfect record of both wins and clean sheets at the halfway stage of the groups.
Another victory on Wednesday could see them keep four Champions League clean sheets on the bounce for the first time since April 2018 and win four Champions League games in a row for the first time since March 2009.
Klopp's side will be firm favourites too considering the ease with which they swept Atalanta aside in the reverse leg, plus their formidable home record - it is now 54 matches across all competitions since Liverpool were beaten at Anfield inside 90 minutes, stretching back to September 2018.
Atalanta will know that they need a vastly-improved performance from the reverse fixture if they are to end that streak, but they do not arrive at Anfield in particularly good form.
Gian Piero Gasperini's side have only won one of their last six games since beating FC Midtjylland in their Champions League opener, and even the goals seem to have dried up for a club that has been one of Europe's most entertaining and prolific teams in recent times.
Atalanta have averaged only one goal per game in that six-match streak, having netted 18 in their five games before that, and barely laid a glove on a patched-up Liverpool backline in Bergamo.
That defeat ended a run of 10 successive Champions League games in which they had scored and they have never gone back-to-back games without finding the net in their admittedly short history in the competition.
Gasperini's men also drew a blank on Saturday when they were held to a goalless draw by Spezia, leaving them seventh in the Serie A table.
Another loss on Wednesday may see their stay in this season's Champions League be a brief one, with an away trip to face Ajax looking like it could be the decider for second place, but they recovered from a far worse situation last season when they still managed to reach the knockout stages despite losing their opening three games.
As it is, Atalanta already have four points to their name this season courtesy of victory at Midtjylland and a come-from-behind 2-2 draw with Ajax, and they arrive at Anfield on a run of three successive Champions League away wins, scoring at least three goals in each of them.
Liverpool Champions League form: WWW
Liverpool form (all competitions): WWWWDW
Atalanta BC Champions League form: WDL
Atalanta BC form (all competitions): LDWLDD
Liverpool should be able to welcome Mohamed Salah back into their side after he returned a negative coronavirus test, with a positive test during international duty ruling him out of the Leicester win.
Salah has scored in each of his last four Liverpool appearances, including in his last two in the Champions League.
It is Diogo Jota who is the man of the moment when it comes to goals for Liverpool, though; the summer signing scored a hat-trick in the reverse fixture to catapult him to the top of the Champions League scoring charts, and another goal on Wednesday would see him become the fastest player to score five goals in the competition for the club.
Despite Salah's possible return, Liverpool could still be without as many as nine players through injury.
Rhys Williams should be fit after suffering a hip injury on international duty and he could come straight into the starting XI if Klopp chooses to rest Fabinho after he played the full 90 minutes in his first game back after injury at the weekend.
Considering such a lengthy injury list, Liverpool's relatively comfortable situation in the group and a 12.30pm kickoff on Saturday, Klopp could opt to rest one of his four main attackers, with Sadio Mane seemingly first in line.
There was good news on the injury front at the weekend, though, with Robin Gosens, Marten de Roon, Jose Luis Palomino and Pierluigi Gollini all returning during the goalless draw with Spezia at the weekend.
Duvan Zapata has been directly involved in five goals in five Champions League group games for Atalanta, with three of those goals coming in three appearances this season.
Liverpool possible starting lineup:
Alisson; N Williams, R Williams, Matip, Robertson; Jones, Wijnaldum, Milner; Salah, Firmino, Jota
Atalanta BC possible starting lineup:
Gollini; Toloi, Palomino, Djimsiti; Hateboer, Pasalic, Freuler, Mojica, Gomez; Zapata, Muriel
We say: Liverpool 3-1 Atalanta BC
Liverpool are unlikely to have things as easy as they did in Bergamo, but their performance in that match, coupled with their record at Anfield, makes it impossible to back against them even with their injury troubles.
Atalanta certainly have the firepower to test Liverpool's defence more than they did in the reverse fixture, but Wednesday's hosts have actually looked more solid at the back since Van Dijk's injury and should have more than enough to seal their place in the knockout stages with victory here.