The Reds were emphatically thrashed by their Premier League rivals after Sadio Mané's dismissal before half-time, but cannot afford to dwell on their disappointment as they prepare for the first game of their continental campaign.
They welcome La Liga side Sevilla, whom they lost to in the Europa League final in Switzerland back in May 2016, in what will prove a tough curtain-raiser on their return to the competition.
This is Liverpool’s first game in the competition since December 2014 and just the second season in the last eight in which they have had Champions League football.
While Sevilla are not to be underestimated, behind only Real Madrid and Barcelona in the Spanish top-flight table this term having finished fourth last season, Liverpool will back expected to progress with NK Maribor and Spartak Moscow their other opponents.
But they must first focus on the challenge of facing the Andalusian side - who are yet to taste defeat in any competition under new boss Eduardo Berizzo.
Just as Liverpool had to overcome TSG 1899 Hoffenheim in the play-off qualifying round, Sevilla beat Turkish team İstanbul Başakşehir over two legs - winning 2-1 away from home before a 2-2 home draw saw them advance 4-3 on aggregate.
They have also claimed two wins and a draw from their opening three league games, including an emphatic 3-0 victory over Eibar most recently - with striker Wissam Ben Yedder continuing his strong start with three goals in four games, including two in the Champions League.
While a different outfit from the one that denied them long overdue silverware, and a return to this competition, in the Europa League final two years ago - Liverpool will still be aware that Sevilla are a dangerous attacking team.
The hosts will be hoping for a repeat of Hoffenheim's trip to Anfield last month. Despite the danger of the German side's fast-paced pressing style, Liverpool fired three goals in the first 21 minutes to virtually end the tie, with the Anfield atmosphere having a clear impact on the visitors while their fluent attacking proved lethal.
Sevilla are a more experienced team on the continent, winning the Europa League for three successive seasons between 2013 and 2015, but this is just their fifth appearance since the Champions League was rebranded in 1992.
Jürgen Klopp's charges will look to replicate the electric start of their win over Hoffenheim, with a fiery atmosphere guaranteed, as they look to get back to winning ways and put the humiliation of their defeat at City beyond them as quickly as possible.
Playmaker Philippe Coutinho could make his first appearance of the season for Liverpool.
The Brazilian was left out of the squad to face City after returning to first-team training just last week after a summer-long saga in which he submitted a transfer request in an effort to join Barcelona.
Klopp has confirmed that Coutinho is a part of his plans, while also revealing the goalkeeper Loris Karius will start over first-choice Simon Mignolet as he looks to rotate his shot-stoppers across the club's several competitions.
Sadio Mané is available, but his three-match domestic ban will be upheld despite Liverpool's attempts to reduce the length. His ban keeps the Senegalese forward out of this weekend’s visit of Burnley before back-to-back trips to Leicester City in the Premier League and the League Cup.
Liverpool are hoping to be able to call upon in-form winger Mohamed Salah, who was withdrawn after 45 minutes against City and was sent home from training with illness on Tuesday afternoon.
Visitors Sevilla will be without Nolito, who picked up a thigh injury at the weekend. The ex-City winger had scored in the win over Eibar on Saturday but later had to be withdrawn.
Fellow summer signing Johannes Geis has not travelled to Merseyside. The midfielder, who signed on loan from Schalke on deadline day, played the final three minutes in their last league match but has not been included in their travelling 23-man squad.
Familiar faces include another former City attacker, Jesús Navas, and ex-Stoke City midfielder Steven N'Zonzi. Only five members of the 18-man match-day squad that took on Liverpool last May remain at the club.
Sevilla's full 23-man travelling squad
Goalkeepers: Sergio Rico, David Soria, Juan Soriano.
Defenders: Gabriel Mercado, Sébastien Corchia, Daniel Carriço, Nicolás Pareja, Simon Kjær, Clément Lenglet, Sergio Escudero.
Midfielders: Guido Pizarro, Steven N'Zonzi, Éver Banega, Franco Vázquez, Ganso, Michael Krohn-Dehli, Pablo Sarabia, Jesús Navas, Walter Montoya.
Attackers: Luis Muriel, Wissam Ben Yedder, Joaquín Correa.
Recent form (all competitions):
Manchester City 5-0 Liverpool
Sevilla 3-0 Eibar (Ganso 46, Ben Yedder 76, Nolito 90+2)
Liverpool and Sevilla's only previous meeting was in the 2015-16 final of the Europa League.
Liverpool have not reached the Champions League knockout rounds since 2008-09, having also progressed from the group stages in the four previous seasons.
The Reds have failed to win any of their last five group games in the competition, winning just one of their six matches in the 2014-15 season - at home to Ludogorets Razgrad.
Liverpool have won their opening Champions League group game in all of their last three campaigns.
Jürgen Klopp has only failed to reach the knockout rounds in one of his four seasons as a manager in this competition, doing so in all of the last three.
Sevilla have reached the next stage in three of their four Champions League appearances, though have never progressed past the round of 16.
The Andalusians have lost just two of their last nine games in this competition.
This will be the first Champions League game Sevilla boss Berizzo has managed in, though he took Celta Vigo to the Europa League semi-finals last season – his only previous European campaign.