Having defeated RB Leipzig in Germany before the international break, Lyon make their second trip in quick succession sitting level on points with group leaders Zenit St Petersburg.
Having avoided the big-hitters in August's draw, Benfica boss Bruno Lage would have hoped that his side would have been in a strong position to earn a place in the last 16 heading into matchday three.
However, back-to-back defeats to RB Leipzig and Zenit have left the Portuguese giants three points adrift at the bottom of Group G, with four separating them and second spot.
While no team has registered successive wins, Benfica have effectively been left requiring at least eight points from their remaining four matches to put themselves in contention for a spot in the knockout rounds.
Lage was witnessed his team struggle for goals in recent league matches, although a 4-0 triumph over Cova Piedade in the Taca de Portugal will at least have provided the team with extra belief heading into Wednesday's contest at Estadio da Luz.
The appointment of Garcia was not roundly welcomed by supporters on social media, and a goalless draw at home to Dijon on Saturday has not helped the new manager in his quest to win over the fans.
Nevertheless, Lyon travel to Portugal aware that most of the pressure is on their hosts, a scenario which could help this talented squad put on the type of performance which is expected of them on a regular basis.
Manchester United may potentially have interested observers in the stands, with the Premier League giants allegedly keeping tabs on the development of Benfica centre-back Ruben Dias and Lyon forward Moussa Dembele.
Benfica form: LWDWLW
Lyon form: LDLWLD
Memphis Depay was absent for Lyon at the weekend as he continues to recover from a thigh problem, although the Netherlands international will hope to be involved on Wednesday.
Bertrand Traore is in contention to come into the team as a replacement for Martin Terrier, while Jeff Reine-Adelaide will be keen to be handed an immediate recall after only featuring off the bench at the weekend.
Lage will feel obliged to select an attacking starting lineup, which should mean another start for playmaker Adel Taarabt.
Benfica possible starting lineup: Vlachodimos; Tavares, Dias, Jardel, Grimaldo; Fejsa, Pires; Pizzi, Taarabt, Vinicius; Seferovic
Lyon possible starting lineup: Lopes; Tete, Marcelo, Denayer, Marcel; Mendes, Toussart, Aouar; Cornet, Dembele, Traore
We say: Benfica 1-2 Lyon
With Benfica under pressure to produce a result and Lyon's players keen to impress their new boss, this could turn out to be a closely-fought contest. However, we are backing Lyon to come out on top, potentially due to a late goal.