The Red Devils travel to their bitter rivals 16 points adrift of them less than halfway through the current campaign, with a defeat on Merseyside likely to spell the end of Jose Mourinho’s increasingly slim title hopes at Old Trafford.
Their hosts look set for a serious title challenge and victory over United will see them return to the summit, ahead of champions Manchester City after the latter usurped them on Saturday.
In all competitions, the visitors have won just two of their past seven games and could end the weekend 11 points behind the Champions League qualification spots if they slump to another defeat.
But Klopp is not expecting the Red Devils to roll over, adamant their manager simply will not stand for anything less than a motivated performance against arguably their biggest historical rivals.
“I cannot think of another manager that would relish coming to face us as much as Jose,” the Reds manager said in his programme notes.
“It is without question we will face the most motivated opponent we will come up against all season, so for us nothing short of our best will be enough.”
Liverpool were unable to get the better of their opponents in the same fixture last year as both teams played out a scoreless draw at Anfield.
However, United subsequently won the return fixture at Old Trafford 2-1, thanks to an early brace from Marcus Rashford.
The Reds have in fact failed to defeat the Red Devils domestically since March 2014, when Steven Gerrard notched a double and Luis Suarez got in on the act in a 3-0 win at Old Trafford.
They did however defeat United 2-0 in the first leg of a Europa League last 16 tie in 2016, to help them to a 3-1 aggregate victory on their way to reaching the final.
In that instance, goals from Daniel Sturridge and Roberto Firmino proved the difference under the lights in front of the Kop.