Liverpool are determined to stretch their unbeaten league record in Merseyside derbies to 13, while curtailing Everton's excellent form in the first Premier League game of the weekend.
Should the Reds avoid defeat in Saturday's early kick off, they will equal their best run of top-flight matches without losing to Everton, set in 1978.
The visitors to Anfield have been in good shape, though, suffering just one defeat in their last 12 fixtures in the division.
Both sides have been hampered by injuries leading into the 228th edition of the rivalry, with Jurgen Klopp and Ronald Koeman needing to alter their preferred strategies.
Adam Lallana's thigh injury, picked up on England duty, is expected to rule him out for around four weeks.
Klopp: Brazil want to play like Liverpool
Klopp can't restore Jordan Henderson into midfield to soften that blow, with the captain suffering a setback in his rehabilitation from a foot injury.
Daniel Sturridge will also not feature having not returned to team training yet.
There are no fitness concerns over Philippe Coutinho or Roberto Firmino, who were flown back to Merseyside in a private jet following their exertions with Brazil, but how fresh the pair will be remains to be seen.
Neither side have any suspension concerns.
LIVERPOOL POTENTIAL STARTING LINE-UP
The loss of Lallana is a gigantic one for the Reds, with the 28-year-old instrumental in helping set their tempo as well as sparking their efforts to regain possession.
Without the ability to restore Henderson in front of the centre-backs, the safest option for Klopp at the base of midifeld would be Lucas.
The Brazilian has featured in 16 Merseyside derbies, and as such, has the experience to navigate what is guaranteed to be an intense affair.
The Liverpool boss could also opt to keep Emre Can as the No.6, using Coutinho alongside Gini Wijnaldum and introducing Divock Origi into the attack.
Alternatively, James Milner can be moved centrally with Alberto Moreno coming in at left-back. The Spaniard last started a game on January 28, though.
Likewise, Marko Grujic is also technically an option, but has not been in the squad for a Premier League game since November 19.
There is the prospect of fielding young Trent Alexander-Arnold at right-back with Nathaniel Clyne on the opposite flank and Milner shifting into the middle.
Klopp has a variety of ways he could tweak things on Saturday, but whatever line-up he selects will be expected to be assertive and cut out supply to Romelu Lukaku.
EVERTON TEAM NEWS
Koeman is convinced his charges are edging closer to inflicting derby defeat on their neighbours.
The Blues have slashed the 16-point advantage Klopp's side held over them in the league at the turn of the year to just six, which partly explains the Dutchman's confidence.
“There has been a big difference in many years in derby results, but I think we are now more close to Everton beating Liverpool," he said.
“We had a good game at home [the reverse fixture in December] and were only defeated by a goal in the 97th minute.
“The team will be ready on Saturday to give Liverpool a big challenge.”
Lukaku will be central to that ambition, with the Belgian striker proving troublesome for the Reds' rearguard in the past, although he last scored at Anfield in 2013.
Koeman has admitted his frustration, though, that "the moment we get the chance to make this season special, we have lost some important players."
Ramiro Funes Mori and Seamus Coleman will not feature again this season after picking up injuries on international duty.
Morgan Schneiderlin sits out with a calf problem, while Yannick Bolasie hopes to return from anterior cruciate ligament damage before the end of the year.
BEST OPTA MATCH FACTS
Liverpool are unbeaten in their last 12 league encounters with Everton (W5 D7 L0). Only once before have they gone on a longer undefeated run against their neighbours (13 games between 1972 and 1978).
Jurgen Klopp could become the first Liverpool manager to win his first three league Merseyside derbies against Everton.
Romelu Lukaku has scored five times against Liverpool in the Premier League, but only one of those goals has come at Anfield (February 2013 for West Brom).
TV COVERAGE & KICK-OFF TIME
Kick off is at 12:30 BST with the match televised live on Sky Sports.