The Red Devils got off to the perfect start in the group stage, beating Paris Saint-Germain on the road in gameweek one.
They head into this game off the back of a clean sheet in the Premier League against Chelsea and will be hopeful of another positive result.
Leipzig saw off Istanbul Basaksehir in their opener and will aim to take a big step towards qualification with all three points at Old Trafford.
Here’s everything you need to know:
The match kicks off at 8pm on Wednesday 28 October at Old Trafford.
What TV channel is it on?
The game is being broadcast on BT Sport 2 and BT Sport Ultimate.
Subscribers can also stream the match via the BT Sport website as well as the BT Sport app.
United won in Paris a week ago
Anthony Martial is back available and should return to the starting XI. Axel Tuanzebe, hero of Paris, could also return but Paul Pogba looks likely to miss out once again.
New boy Donny van de Beek is pushing for inclusion and could play if Bruno Fernandes is rested ahead of Arsenal.
The visitors will be without Lukas Klostermann, Nordri Mukiele, Konrad Laimer and Amadou Haidara.
Manchester United: De Gea, Tuanzebe, Lindelof, Maguire, Wan-Bissaka, McTominay, Fred, Telles, Fernandes, Rashford, Martial
RB Leipzig: Gulacsi, Orban, Upamecano, Adams, Halstenberg, Nkunku, Olmo, Forsberg, Kampl, Angelino, Poulsen
Leipzig are a quality side and will present United with significant problems. That said, United delivered on the biggest stage last week against PSG and will be hopeful a similar level of performance can bring with it an equally positive result. Manchester United 2-1 RB Leipzig