The La Liga outfit prevailed 3-0 in the first leg in Spain, leaving their opponents requiring one of their all-time greatest European performances to remain in the competition.
Match preview
Given Sevilla's resurgence under Jorge Sampaoli, they were clear favourites to emerge victorious when they played host to the Dutch giants last week.
That said, the manner of their victory was unforeseen, three goals in the space of 10 minutes either side of half time earning Los Nervionenses a likely tie-winning triumph.
Although Sevilla's home form has been considerably better than their efforts on their travels, they brushed PSV aside in a way which suggested that they believe that they can win this tournament for a seventh time in their history.
The success over PSV was backed up by a 1-1 draw at Champions-League chasing Rayo Vallecano at the weekend, although Sevilla only sit three points clear of the La Liga relegation zone.
Sevilla have now failed to post an away win over a club other than lower-level opposition in the Copa del Rey since October 15, a streak which needs to change if they want to end their campaign on a high.
While PSV suffered a double blow in January with the exits of Noni Madueke and Cody Gakpo, there is still enough talent at the club to win the Eredivisie and go deep in this competition.
However, given the capitulation in Spain and the 2-2 draw at FC Utrecht which followed on Sunday, Ruud van Nistelrooy cannot be feeling overly confident about the progression of his team.
The latter of those results has left PSV six points off top spot in the Dutch top flight and just three points above fifth-placed FC Twente, who they face on Sunday.
Although Van Nistelrooy will no doubt be focused on this contest, consideration will have to be given to the weekend if they cannot make a sufficient dent in Sevilla during the opening hour.
PSV Eindhoven Europa League form:
W
W
L
W
W
L
PSV Eindhoven form (all competitions):
W
D
W
W
L
D
Sevilla Europa League form:
W
Sevilla form (all competitions):
L
W
L
W
W
D
Team News
Van Nistelrooy is expected to make changes to his PSV starting lineup on the back of the last two results, with Johan Bakayoko in line to start on the flank.
Phillipp Mwene could return at right-back, while Xavi Simons may switch to the role behind Luuk de Jong if Thorgan Hazard is able to shake off a muscle issue.
Anwar El Ghazi remains with a similar problem and is also battling to be fit for this contest.
Sevilla will be unable to call upon Erik Lamela after the playmaker collected his third European caution of the season in the first leg.
With Loic Bade sidelined with a biceps injury, Fernando could again deputise in the back three, although Nemanja Gudelj is able to return after serving a domestic ban.
PSV Eindhoven possible starting lineup:
Benitez; Mwene, Ramalho, Branthwaite, Van Aanholt; Til, Sangare, Veerman; Bakayoko, De Jong, Simons
Sevilla possible starting lineup:
Bounou; Nianzou, Fernando, Gudelj; Navas, Jordan, Rakitic, Acuna; Torres, Gil; En-Nesyri
We say: PSV Eindhoven 2-1 Sevilla
While we do not see Sevilla exiting the competition on Thursday, they may wish to manage the game in a professional manner. That could allow PSV to win on the night, but the visitors should still progress on aggregate in comfortable fashion.
How to watch
You can watch PSV Eindhoven vs. Sevilla and every MLS match this season live on Apple TV. Click here for more details on how to subscribe.
For data analysis of the most likely results, scorelines and more for this match please click here.