The Red Devils made a brilliant start to the group stage, beating Paris Saint-Germain away and downing Leipzig 5-0 at Old Trafford, but since then, defeats to Istanbul Basaksehir and PSG at Old Trafford have left qualification in the balance.
Leipzig need a win to progress, unless PSG lose to Basaksehir, so there will be no lack of motivation from their side.
Their form has been somewhat patchy of late, with two wins in their last five in all competitions, defeat to PSG and draws with Bayern Munich and Frankfurt in the BUndesliga.
What time is RB Leipzig vs Manchester United?
The match kicks-off at 8pm on Tuesday 8 December at the Red Bull Arena.
What TV channel is RB Leipzig vs Manchester United on and is there a live stream?
BT Sport 2 will be showing the game live with coverage starting at 7pm.
Subscribers can stream the action on BT Sport Player or on the BT Sport app.
Manchester United are missing Edinson Cavani and Anthony Martial for this one, while Phil Jones remains out.
Luke Shaw and David de Gea are back to fitness and available.
RB Leipzig vs Manchester United odds
7/5 RB Leipzig
9/5 Man Utd
Odds courtesy of Betfair