The Greek side recorded an impressive 2-1 win over the Hammers in the reverse fixture on matchday three to blow Group A wide open, ending West Ham's English-record 17-game unbeaten run in Europe.
Match preview
Defeat in Piraeus contributed to a concerning run of form West Ham now find themselves in, as another defeat over the weekend means David Moyes's side have now lost four of their last five games.
Just days after a famous EFL Cup win over Arsenal here at the London Stadium, West Ham quickly returned to losing ways, going down 3-2 to another club from the capital - Brentford.
The manner of Saturday's defeat will have been very disappointing for Moyes too, as his side led 2-1, and Michail Antonio squandered a glorious chance to put them 3-1 up.
A lack of defensive solidity is evident in the West Ham defence, as they have conceded 11 goals during this poor run of form, seeing them slip to 11th in the Premier League despite a very good start which saw them taken 10 points from their opening four games.
In the seven games since, the Hammers have taken just four points, losing five, while a defeat in Europe last time out has also put increased pressure on this fixture.
That matchday three defeat to Olympiacos was not wholly damaging as they remain top of the group, but they are now level on points with Freiburg, who face bottom-placed TSC Backa Topola this week, so another defeat would likely see them drop out of the top two.
A win for the visitors here would be a remarkable feat, just like their win was in Greece two weeks ago, as in West Ham's 17-game unbeaten run, they had won 16 of those games.
It also kept alive Olympiacos' hopes of progression, as a defeat would have left them a long way adrift even at the midway point.
Manager Diego Martinez will have been extremely frustrated at how they threw away two points in drawing with TSC on matchday two having led 2-0, while also losing late on at home to Freiburg in their group opener.
However, Kostas Fortounis and Rodinei goals saw them win 2-1 over the Hammers, and they should travel to London with some belief.
It may also help psychologically that Olympiacos have a very impressive recent record in the English capital, winning on their previous two trips - both against Arsenal in this competition.
Youssef El Arabi's astonishing 120th-minute winner in the round of 32 back in 2020 was one of the most dramatic moments in the competition's recent history, while it was the Moroccan who scored the winner again the following the season in the last 16, but on that occasion Olympiacos still went out 3-2 on aggregate.
While the West Ham win should give the side the belief that they can win here, they will enter the game with their confidence in tatters after a humiliating defeat at home to PAOK Salonika over the weekend.
PAOK were 4-0 up at an empty Georgios Karaiskakis Stadium at one point, and late goals from Fortounis and Georgios Masouras did little to make the scoreline look more respectable.
Their previous home league outing proved even more damaging too, as their clash with Panathinaikos was abandoned after visiting substitute Juankar was dazed by a firecracker, leading to the game being awarded to the away side and Olympiacos being docked a point and forced to play two games behind closed doors for the trouble.
That decision from the Greek footballing authorities leaves Olympiacos four points adrift of Pana, who lead the way, with AEK Athens and PAOK also both in hot pursuit.
West Ham United Europa League form:
W
W
L
West Ham United form (all competitions):
D
L
L
L
W
L
Olympiacos Europa League form:
D
W
W
L
D
W
Olympiacos form (all competitions):
W
W
D
W
W
L
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Team News
Kurt Zouma failed a late fitness test for West Ham's trip to Brentford over the weekend, but could return to the squad here.
Both Lucas Paqueta and Edson Alvarez will be available again after serving suspensions at the weekend for picking up five domestic bookings.
This season's cup goalkeeper Lukasz Fabianski was unavailable for the trip to Piraeus but has since returned and featured in the EFL Cup win versus Arsenal, so he should replace Alphonse Areola from the weekend's side.
Moyes has gone strong with his team selections in this competition so far, and given the importance of getting a win, Paqueta and Jarrod Bowen both may start.
Mohammad Kudus has started all three Europa League games so far, netting two on matchday one against TSC, and he is the man in-form for the hosts, having scored in both of his last two games, including a stunning acrobatic strike at Brentford.
Olympiacos will be able to call upon Andreas Ntoi again on the continent after he missed the reverse fixture following a sending off against TSC.
Ntoi's return will be of great help to Martinez, as the Greek side have a long list of players out injured, including Athanasios Androutsos and UNAM-loanee Nicolas Freire, who has featured in five of their Europa League games so far.
Omar Richards will not feature on his potential return to England, as the Nottingham Forest loanee is yet to make his debut for the club, and Giulian Biancone, who made the same move this summer, is in the same boat.
After returning from respective loan spells over the summer, both Bandiougou Fadiga and Doron Leidner are yet to feature for Olympiacos this term.
West Ham United possible starting lineup:
Fabianski; Kehrer, Mavropanos, Aguerd, Cresswell; Ward-Prowse, Soucek, Lucas Paqueta; Kudus, Bowen, Benrahma
Olympiacos possible starting lineup:
Paschalakis; Rodinei, Porozo, Retsos, Ortega; Alexandropoulos, Camara, Hezze; Podence, Jovetic, Fortounis
We say: West Ham United 3-1 Olympiacos
The West Ham faithful will be in expectant mood that they can turn the tide on a poor recent run of form, despite losing to the Greeks in Piraeus two weeks ago.