The Greek side are on a seven-game unbeaten run at home in all competitions as they entertain the team bottom of Group C knowing that a place in the last 16 is within touching distance.
Anderlecht have struggled in this year's competition. Indeed, one point from five games means the Belgian champions cannot qualify for the Europa League and will finish bottom of a group for the fifth time.
Olympiakos won their previous meeting 3-0 in October and go into the match level on points with Benfica knowing victory will see them finish runners-up behind Paris Saint-Germain by virtue of a better head-to-head record.
However, Olympiakos will have to do without top scorer Kostas Mitroglou as he remains sidelined with a knee injury.
The 25-year-old attacker has scored 23 competitive goals this season for club and country – including a hat-trick against Anderlecht in Belgium – but he injured his medial collateral ligament during their defeat to PSG and is set for a month out of action.
Michel's side came through their 2-0 win over Asteras Tripolis on Saturday without any new injury worries, though, so Mitroglou is the only man missing.
Javier Saviola and Kostas Manolas were both rested ahead of the clash, while Gaetan Bong and Michael Olaitan were left on the bench.
Having been knocked out of the Coupe de Belgique to Westerlo, Anderlecht bounced back to winning ways with victory over Waasland-Beveren on Saturday.
Anderlecht sit third in the Pro League, but it is on the European stage where they have struggled. The Belgium side travel to Greece with no win away from home in their last six Champions League fixtures.
John van den Brom also has one player out through injury – Matias Suarez – while 20-year-old striker Massimo Bruno will miss the match through suspension.