Meanwhile, the Cypriot side will be in high spirits after their 2-1 win against PAOK last week, despite still sitting at the bottom of Group E.
Following their 1-0 win against Granada on matchday five, both PSV and the Spanish outfit have managed to qualify for the knockout stages, with the Dutch side just one point behind the current group leaders.
This means that Roger Schmidt's men could still top their group if they gain either a win or a draw this Thursday, depending on the outcome of Granada's upcoming game against PAOK.
Domestically, PSV have experienced a strong start to their 2020-21 season, with the Red and Whites currently occupying third spot in the Eredivisie.
However, they will be hoping to bounce back from a disappointing 2-2 draw against Heerenveen at the weekend, with PSV nearly suffering a shock defeat against their opponents, before Joel Piroe netted the equaliser late in extra time.
If the hosts manage to secure a victory in their upcoming European fixture, it will be the first time PSV have recorded back to back home Europa League wins since February 2012, having beaten PAOK 3-2 in their previous home game.
Omonia, on the other hand, find themselves at the bottom of their group as they head into matchday six, having picked up just one win in their debut season of the competition.
In the Cypriot First Division, Henning Berg's men currently sit sixth, and their previous league result ended in a comfortable 3-0 win against APOEL.
If they pick up an unlikely win against PSV in midweek, they could jump into third spot in Group E - leapfrogging PAOK, with the Greek outfit potentially coming in last.
However, it is worth noting that Omonia's only previous away match in a major European competition against a Dutch side was when they faced Ajax in the European Cup back in 1979, where they were beaten 10-0 by the Amsterdam outfit.
These two sides have only faced each other once - during the reverse fixture, where PSV were able to gain a 2-1 win over their opponents.
PSV Eindhoven Europa League form: WWLWL
PSV Eindhoven form (all competitions): DWWWDW
Omonia Europa League form: WLLLD
Omonia form (all competitions): WWDLLD
The hosts will also be without long-term absentee Marco van Ginkel as the midfielder continues to recover from his knee injury.
As for Omonia, the visitors currently have no fitness worries heading into this game, with Berg able to choose from a fully fit squad.
The Norwegian coach could opt for the same starting XI that managed an impressive victory against PAOK last time round.
PSV Eindhoven possible starting lineup:
Mvogo; Dumfries, Teze, Boscagli, Max; Gotze, Rosario, Sangare, Gakpo; Madueke, Malen
Omonia possible starting lineup:
Fabiano; Loizou, Hubocan, Luftner, Lang, Kiko; Sene, Gomes, Kousoulos, Tzionis; Kakoullis
We say: PSV Eindhoven 2-0 Omonia
PSV should be able to pick up a comfortable victory at home against Omonia, with the Dutch side hoping to top their group in the competition. Although the visitors managed a positive result against PAOK last time round, they have struggled in their previous group games, therefore a win on Thursday seems highly unlikely.