As for the visitors, they are likely to require back-to-back victories in order to progress as runners-up in Group G.
While Julian Nagelsmann would have recognised that his team had been drawn in a group with three clubs of similar quality, the RB Leipzig head coach would have been confident that their attacking qualities could potentially make the difference by the end of the group.
As it stands, that is how it has panned out with the German side claiming three wins from their four games, including twice on the road against Benfica and Zenit St Petersburg.
Leipzig now have the opportunity to reach the knockout stages of the Champions League for the first time in their history, with victory on Wednesday evening potentially sealing top spot in Group G.
Nagelsmann's outfit have also netted 16 times in their last three domestic games, a return which has helped put Leipzig to within one point of Bundesliga leaders Borussia Monchengladbach.
Benfica have been far less impressive than their hosts, although the Portuguese team still sit two points clear at the top of their domestic standings.
While eight league triumphs have been recorded in succession, Benfica needed to come from behind to earn a narrow 2-1 success at Santa Clara before the international break.
That said, the desire shown in that match may stand Bruno Lage's team in good stead as they bid to avoid a defeat which may even leave them out of contention for a spot in the Europa League.
Lage will also take confidence from his side having scored at least once in each of their previous four outings in this group, with their five strikes coming from four different players.
RB Leipzig form: LWWWWW
Benfica form: WWWLWW
Chelsea loanee Ethan Ampadu is in line to make his first Champions League start for RB Leipzig this week.
The remainder of the team could stay the same, although Kevin Kampl is pushing for a start after recovering from a minor injury.
As for Benfica, they will be without Haris Seferovic, who sustained an injury while on international duty with Switzerland.
Carlos Vinicius, who has five league goals to his name this season, is likely to replace him in attack.
RB Leipzig possible starting lineup: Gulacsi; Klostermann, Ampadu, Upamecano, Halstenberg; Laimer, Demme; Sabitzer, Forsberg; Nkunku, Werner
Benfica possible starting lineup: Vlachodimos; Almeida, Dias, Jardel, Grimaldo; Pizzi, Luis, Pires, Cervi; Chiquinho, Vinicius
We say: RB Leipzig 3-1 Benfica
We can only see one winner here. RB Leipzig are regarded as the dark horses in this competition and they will relish the chance to seal their place in the knockout stages with a game to spare. Benfica, on the other end, have shown too many frailties in their previous outings.
body check tags ::