Despite the bonus of scoring two away goals in the first half, a late fourth for the Greek outfit has given the visitors an advantage ahead of the reverse fixture.
With PSV only regarded as outsiders for the Eredivisie title, Roger Schmidt is under pressure to have an extended run in this competition.
However, the 4-2 defeat in Greece has left PSV with an uphill task on Thursday, particularly with their recent defensive performances leaving a lot to be desired.
Nine goals have been conceded in four matches, one of which came at the weekend when PSV had to come from behind to claim a 3-1 victory over Vitesse.
Schmidt's side have now won two of their last six matches, a run which will inevitably need to improve if the German is to keep his job in the dugout.
The biggest plus in recent weeks has been the form of Donyell Malen, who has provided two goals or assists in three of his last five appearances.
As far as Olympiacos are concerned, their eye-catching triumph last week has come between disappointing results against Panathinaikos and Aris.
Failure to win either of those fixtures will act as a reminder to Pedro Martins that his side is susceptible to complacency, something which must be avoided in the Netherlands.
Giorgos Masouras's late goal in the first leg has given Olympiacos control of this tie, but they are without a clean sheet in four games in all competitions.
While the return of Ruben Semedo from suspension could prove key, there is a feeling that Martins's side will need to get on the scoresheet to maintain their advantage in this tie.
PSV Eindhoven Europa League form: WLWWWL
PSV Eindhoven form (all competitions): LWLDLW
Olympiacos Europa League form: W
Olympiacos form (all competitions): WWWLWD
Martins will hand a recall to Semedo in a move which will likely see Sokratis Papastathopoulos drop down to the substitutes' bench.
Masouras could get the nod over Mathieu Valbuena after coming off the bench to score a decisive goal last week.
PSV Eindhoven possible starting lineup:
Mvogo; Dumfries, Teze, Boscagli, Max; Rosario, Thomas; Gotze, Thomas; Zahavi, Malen
Olympiacos possible starting lineup:
Sa; Lala, Semedo, Ba, Reabciuk; M'Vila, Bouchalakis; Masouras, Camara, Bruma; El-Arabi
We say: PSV Eindhoven 3-1 Olympiacos
There have been goals aplenty in PSV's recent matches, something which we expect to continue on Thursday night. While we do not anticipate the Dutch outfit keeping a clean sheet, Schmidt's side have the firepower to make the difference at the other end of the pitch, potentially helping the club through to the next stage by the closest of margins.