Salah and the club confirmed last week that he will be heading for pastures new, bringing an end to his trophy-laden nine-year stint at Anfield.
Fittingly, Liverpool's first game since Salah's announcement sees them take on one of the Reds' great rivals of the last decade.
Manchester City await in an FA Cup quarter-final at the Etihad Stadium, with a place at Wembley up for grabs.
Man City might be trailing Arsenal by nine points in the Premier League, but Pep Guardiola's team got one over on the Gunners before the international break.
City were deserved victors in the EFL Cup final, with Nico O'Reilly's double capping a 2-0 win. And having clinched the first major trophy on offer this season, Guardiola's men will now be eager to book an immediate return to Wembley.
It promises to be a thriller. Here, we delve into the key Opta insights.
What's expected?
In years gone by, Man City versus Liverpool has been English football's go-to rivalry, and while the stakes are perhaps not quite as high now as they were in the Jurgen Klopp-Guardiola era, these teams still know how to serve up a cracker, as they did in a 2-1 win for City at Anfield in February.
This will be the seventh FA Cup tie between City and Liverpool.
City progressed from the first two after replays in 1955-56 and 1972-73, but the Reds have since won each of the last four, most recently in the 2021-22 semi-finals.
Guardiola's team have already completed a Premier League double over Liverpool this season and could win three successive meetings with the Reds in all competitions for the first time since March 1937 (four in a row).
Indeed, the last side to beat Liverpool three times in a single campaign were West Ham in 2015-16.
City are given the edge by Opta's predictive model, which has run 10,000 pre-match data-led simulations.
In 51.1% of those, City come out on top. Liverpool progress in 24.1%, with the remainder requiring extra time and potentially penalties.
Man City building momentum?
Arsenal are heavy favourites to win the Premier League title (Opta's supercomputer rates their chances at 97.5%), but City will not give up hope.
And having already got their hands on the first major trophy on offer this term, City will have a taste for silverware.
Since they are out of the Champions League and the gap in the Premier League is so large, the FA Cup will no doubt be a major aim, especially as doubts over Guardiola's long-term future continue to swirl.
City have won each of their last 31 FA Cup matches outside of semi-finals and finals, since losing to Wigan Athletic in the 2017-18 fifth round.
They are looking to reach the semi-finals for an eighth successive season, with their run of seven straight appearances in the last four already marking a competition record.
City have won each of their last 17 home matches in the FA Cup, while victory here would make this the outright longest home winning run by any side in the competition proper, surpassing Clapham Rovers’ 17 wins from December 1873 to February 1881.
Two of City's seven FA Cup triumphs have come under Guardiola, in 2018-19 and 2022-23, with the latter forming part of their memorable treble.
Salah's long goodbye
Salah will leave not only as a Liverpool legend, but as an undisputed Premier League great.
The 33-year-old has scored in each of his last three FA Cup appearances, including in a quarter-final against Manchester United in 2023-24.
The last player to score in four consecutive FA Cup appearances for Liverpool was Emile Heskey in 2000-01 – whose run included a goal against Manchester City in the fifth round.
This will be Salah's 25th, and last, game against City as a Liverpool player. He has played more times against them during his stint with the Reds than any other player.
Against only Man Utd (22) has Salah recorded more goal involvements than he has against City (21 – 13 goals, eight assists).
Salah missed Liverpool's defeat to Brighton a fortnight ago due to injury, but Slot expects him to be fit to feature here, although this match is likely to come too early for Alexander Isak, who is just back in training following his long injury lay-off.
The Reds' first-choice goalkeeper, Alisson, remains sidelined.
Liverpool, unlike City, have a Champions League quarter-final tie to look forward to, though whether Arne Slot will be relishing a clash with holders Paris Saint-Germain is in question.
However, Liverpool have progressed from 17 of their last 19 FA Cup quarter-final ties, although they lost 4-3 to Manchester United in their most recent in 2023-24.
The Reds have not been eliminated from back-to-back FA Cup quarter-final appearances since 1967-68/1969-70 under Bill Shankly, and this competition is, realistically, their best chance of silverware this term.
Liverpool won 3-1 away at Wolves in the fifth round, but they have not won two away games against Premier League opponents within a single FA Cup campaign since 2005-06, when they won at Portsmouth in the fourth round and Birmingham City in the quarter-finals, going on to lift the trophy.
PLAYERS TO WATCH
Manchester City – Erling Haaland
Haaland, who netted the winner for City at Anfield a couple of months ago, has scored in each of his last three home games against Liverpool in all competitions.
The only Premier League players (since 1992-93) to score in four or more consecutive home appearances against the Reds are Chris Sutton (four from 1994 to 1996) and Sergio Aguero (five from 2013 to 2017).
Liverpool – Dominik Szoboszlai
Szoboszlai was in the thick of it when City won at Anfield a couple of months ago, scoring a brilliant free-kick to put Liverpool ahead, before he was sent off for denying a goalscoring opportunity with the last kick of the game.
The midfielder is one of few Liverpool players to perform up to the high standards expected of them this term. He has registered 20 goal involvements for the Reds in 2025-26, trailing only Hugo Ekitike (23).
Szoboszlai has scored 12 goals from 7.0 expected goals (xG), and his five free-kick goals will have plenty to do with that overperformance. The 25-year-old leads Liverpool for chances created (94), and only trails Salah (nine) for assists, with eight to his name.