While Scott Parker's side have failed to win each of their last seven home games across all competitions, Roger Schmidt's men are seeking to avoid back-to-back away matches without a win for the first time since December.
Match preview
Club Brugge have been the surprise package in this season's Champions League and they will be competing in the knockout rounds for the first time in their history after finishing second in Group B ahead of Bayer Leverkusen and Atletico Madrid.
After winning their first three group games, the Belgian giants failed to win their final three fixtures but they still managed to claim a top-two spot to advance with group winners Porto, keeping a tournament-high five clean sheets in the process.
Despite leading the club into the last 16, head coach Carl Hoefkens was relieved of his duties on December 28 after just six months in charge following a poor domestic run of form, with Scott Parker hired as his successor.
Parker is yet to spark a revival in the Brugge hotseat, though, drawing five of his first seven Belgian Pro League matches in charge including last weekend's 1-1 draw at home against Union SG, and hopes of defending their top-flight title are now all but over as they sit 20 points behind leaders Genk.
Brugge, who have already been eliminated from the Belgian Cup, can now focus fully on their first-ever meeting with Benfica on Wednesday as they bid to continue their fairytale journey in the Champions League.
Blauw-Zwart have previously faced five different Portuguese opponents in European competition including Benfica's rivals Porto both home and away this season, with an impressive 4-0 away victory in September followed by a 4-0 home defeat just two months later.
Benfica, meanwhile, are competing in the Champions League knockout rounds for just the fourth time in the last 11 seasons after topping Group H by the finest of margins.
The Eagles won four of their six group games, including an emphatic 6-1 away victory against Maccabi Tel-Aviv in their final fixture, and they ended up on the same number of points (14) and with the same goal difference (+9) as second-placed Paris Saint-Germain, but they topped the group after scoring more away goals than the Parisian side.
Roger Schmidt's side have since consolidated their place at the Primeira Liga summit, with a run of seven wins in their last ninth top-flight matches keeping them five points clear of rivals and current holders Porto.
However, Benfica's seven-game unbeaten run in all tournaments was brought to an end by Braga in the Taca de Portugal quarter-finals last Thursday. After playing out a 1-1 draw with nine men in 120 minutes, the Eagles lost 5-4 on penalties with Fredrik Aursnes missing the only spot kick.
Benfica will be confident of returning to winning ways against Brugge and getting a foothold in their first-leg tie on Wednesday, as they have won nine and drawn four of their previous 14 meetings with Belgian opposition, while they are also unbeaten in their last seven Champions League games.
Club Brugge Champions League form:
W
W
W
D
L
D
Club Brugge form (all competitions):
D
D
D
W
D
D
Benfica Champions League form:
W
W
D
D
W
W
Benfica form (all competitions):
D
W
W
W
W
L
Team News
Club Brugge trio Tajon Buchanan (knock), Andreas Skov Olsen (hip) and Ferran Jutgla (back) are all doubtful with minor injuries and will be assessed ahead of kickoff.
The potential absence of Buchanan could see Antonio Nusa brought into the starting lineup to operate on the right flank, joining Noa Lang and former Benfica striker Roman Yaremchuk in the front three.
Captain and key playmaker Hans Vanaken is expected to continue in centre-midfield, while Abakar Sylla will be competing with Jack Hendry and Brandon Mechele for a starting spot at centre-back.
As for Benfica, they currently have a clean bill of health so Schmidt will have a fully-fit squad available for the trip to Belgium.
Following the big-money January departure of Enzo Fernandez, Chiquinho has played regularly alongside Florentino Luis in centre-midfield, and both players are expected to continue in the side on Wednesday.
Alexander Bah and Morato are both available for selection despite being shown red cards in the defeat against Braga last week, and the former is expected to retain his place at right-back, joining Nicolas Otamendi, Antonio Silva and Alex Grimaldo in the back four.
Goncalo Ramos will compete with Goncalo Guedes to lead the line in attack, while Rafa Silva will be pushing to start in an advance midfield role ahead of either Aursnes and David Neres.
Club Brugge possible starting lineup:
Mignolet; Mata, Hendry, Mechele, Meijer; Rits, Onyedika, Vanaken; Buchanan, Yaremchuk, Lang
Benfica possible starting lineup:
Vlachodimos; Bah, Silva, Otamendi, Grimaldo; Luis, Chiquinho; Mario, Rafa, Aursnes; Guedes
We say: Club Brugge 1-2 Benfica
Club Brugge have relished their underdog status throughout this season's Champions League and another resilient display is required if they wish to come out on top against a Benfica outfit who also enjoyed an impressive group-stage campaign.