Both sides sit level on points ahead of the crucial clash in Athens on Tuesday night and will be hoping to keep pace with Group C leaders Paris Saint-Germain
The two sides met in Lisbon in the last round of European fixtures, with the Greek club claiming a credible 1-1 draw, but they were only seven minutes away from victory when Oscar Cardozo cancelled out Alejandro Dominguez’s first-half opener.
After three matches in the competition, both sides have four points, but Michel's Olympiakos sit ahead of Benfica due to their neutral goal difference.
Benfica's last trip to the Georgios Karaiskakis Stadium saw them on the wrong end of a 5-1 hammering in the 2008-09 Uefa Cup group stage, but they head to Greece in good form this time around.
Their only defeat in their last 12 matches in all competitions came with a 3-0 loss at Paris Saint-Germain on Champions League matchday 2, while their most recent league fixture ended in a 3-0 away win at Academica on Friday.
Benfica coach Jorge Jesus was satisfied with the win in Coimbra, but ahead of the return to Champions League action he insisted that the club are not prioritising any one competition over another.
He told Sport TV: "The Portuguese league is very important to us, but we make no distinction between one and another competition.
"Our attitude is always the same. We want to win all the competitions and all are important."
Attacker Enzo Perez added: "We now have a decisive match in the Champions League that can decide many things and we want another positive result."
Benfica will have to keep Kostas Mitroglou quiet if they are to keep their hosts at bay, with the Greece international in the form of his life after scoring 16 times - including four hat-tricks - in all competitions so far this season.
Like the Portuguese club, Olympiakos head into the encounter in good form after only one defeat from their last 16 matches in all competitions, with that solitary loss also coming against PSG.
In two of their last three matches, the Greek champions have scored five, with OFI and Fokikos on the wrong end of those defeats, while Saturday's derby with Panathinaikos saw them claim a 1-0 win, with Mitroglou netting the winner late on.
The hosts have a few injury concerns to contend with as Gaetan Bong (foot and hamstring), Paulo Machado (knee) and Ariel Ibagaza (groin) are expected to miss out, while Dominguez (thigh) and Michael Olaitan (hamstring) are doubtful.
Benfica coach Jesus, meanwhile, also has fitness problems to take into consideration, with Guilherme Siqueira, Lazar Markovic, Miralem Sulejmani (all thigh) and Eduardo Salvio (knee) all concerns.