The Portuguese giants prevailed by a 2-1 scoreline when these two clubs met in the reverse fixture last month.
Many Lyon supporters were quick to voice their dissatisfaction when Rudi Garcia was appointed as the club's new manager last month, and the frustration only intensified when the French side suffered disappointment at Estadio da Luz.
However, back-to-back victories over Metz and Toulouse in Ligue 1 have relieved the immediate pressure on Garcia, with the club now up to eighth position in the standings.
While another setback against Benfica would lead to an instant change of mood at the Groupama Stadium, Garcia will have confidence that his side can make it three victories on the bounce.
The Frenchman will be particularly pleased with how Memphis Depay and Moussa Dembele have regained their touch in front of goal, with the pair having contributed six goals between them in the last three fixtures.
Benfica also endured a relatively slow start to the campaign as they suffered defeats to Porto, RB Leipzig and Zenit St Petersburg by the start of October.
Bruno Lage has spearheaded something of a revival, however, with five successive wins being recorded during a period where Benfica have conceded just one goal.
They now sit five points clear at the top of the domestic standings, although Lage is aware that both himself and his players will come under fire if they fail to make the knockout stages of the Champions League for the third consecutive season.
Despite being the club's top scorer, Pizzi will hope to improve in the final third with just three goals coming from his last nine appearances in all competitions.
Lyon form: WLDLWW
Benfica form: LWWWWW
Garcia could retain much of the team which began the win over Toulouse, although there may be alterations to the make-up of the midfield.
Bertrand Traore also influenced the contest, but the former Chelsea man will likely see Depay and Dembele continue their partnership in attack.
Like his Lyon counterpart, Lage may also make minimal changes after Benfica's comfortable 2-0 success against Rio Ave.
Haris Seferovic is the most likely inclusion in attack should Lage opt to tinker with his forward line.
Lyon possible starting lineup: Lopes; Dubois, Andersen, Denayer, Kone; Reine-Adelaide, Mendes, Tousart, Aouar; Depay, Dembele
Benfica possible starting lineup: Vlachodimos; Almeida, Dias, Ferro, Grimaldo; Pizzi, Luis, Pires, Cervi; Chiquinho, Vinicius
We say: Lyon 1-1 Benfica
Neither side have produced their best form on the European stage this season, and we feel that could lead to the two clubs cancelling each other out. However, with a trip to Russia to face Zenit St Petersburg up next, do not be surprised to see Lyon force the game in the latter stages if the scoreline remains level.