The Reds' 2-1 reverse at home to Lyon in the UEFA Champions League on Tuesday was their fourth consecutive loss - their worst run of results for 22 years - and defeat against United would further increase the pressure on manager Rafa Benitez.
As if things couldn't get any worse for Liverpool they face the prospect of going into the must-win match without inspirational captain Steven Gerrard.
The England ace returned to action, having missed the 1-0 defeat at Sunderland last week, against Lyon but lasted just 25 minutes due to the troublesome groin injury he picked up while on international duty.
The hosts will take heart from the fact that they were victorious the last time the Premier League champions visited Anfield with Gerrard and star striker Fernando Torres both on the bench.
Although Red Devils defender Gary Neville insists revenge is not on the cards United must still be smarting over the manner of the defeat at the hands of Liverpool last time out when they were hammered 4-1 at Old Trafford.
United have been dealt an injury blow of their own with the news that Wayne Rooney remains a doubt for the game with a calf strain.
The 23-year-old had said previously that he would miss the game to be at the birth of his first child with the baby expected on the day of the game. However it appears the frontman could be about to miss the match anyway.
United have performed well without Rooney having beaten Bolton 2-1 last weekend and CSKA Moscow on the plastic pitch on Wednesday in the Champions League.
Although both set of players would never admit it victory for United could effectively end Liverpool's title hopes with a possible three points for champions taking them 10 points clear of their rivals and inflicting their fourth Premier League defeat of the season.
Liverpool newsDespite Gerrard being a major doubt, Liverpool do expect to have Torres back after the Spaniard missed the defeats against Sunderland and Lyon with a groin strain.
Glen Johnson was another to miss the Lyon clash with a groin injury but the right-back is hopeful he will recover in time for the visit of United.
Summer signing Alberto Aquilani made his long-awaited first appearance in a Reds shirt when he played 15 minutes for the reserves in midweek but the game on Sunday has come too soon for the Italian international.
Another summer arrival in Sotiros Kyrgiakos is out after suffering a knee injury while playing for Greece earlier this month.
Man Utd newsDespite question marks being raised over Rooney's fitness, United have both Ryan Giggs and Patrice Evra back in contention after the pair missed the Champions League match in Moscow.
However midfielder Darren Fletcher remains a doubt with a knee injury while Park Ji-Sung (knee) looks certain to be ruled out.
Rooney's possible absence could hand Michael Owen the chance to start against his former club although manager Sir Alex Ferguson could opt to use Dimitar Berbatov as a lone striker should Rooney miss out.
Nemanja Vidic came through the clash with CSKA unscathed after missing the Bolton match with an ankle problem so he will start again.
Owen Hargreaves (knees) is nearing full fitness but is unlikely to be named on the bench.
Possible starting XIs:
Liverpool: Reina, Carragher, Skrtel, Insua, Agger, Mascherano, Benayoun, Lucas, Kuyt, Babel, Torres.
Man Utd: Van der Sar, O'Shea, Ferdinand, Vidic, Evra, Giggs, Scholes, Anderson, Valencia, Rooney, Berbatov.