The Lancashire outfit sit 16th heading into the tie, with a recent run of poor form leaving them in no-man's land in the league table with nine games to go.
Alex Neil's men have won just three times in 2021, and have picked up only five points in their previous eight games.
Last time out, they succumbed to a disappointing 2-0 away defeat at Middlesbrough.
Luton Town are three points and two places ahead of their hosts with a game in hand, but similarly have little to play for in terms of league position for the rest of the campaign.
Nathan Jones' side have improved slightly in recent weeks, with three wins and two losses in their last five outings.
The Hatters come into the game off the back of an impressive 2-0 home victory against Coventry City.
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Team news
Preston North End will be without Alan Browne for the game, after their captain picked up a contentious red card in the game against Middlesbrough.
He joins Ryan Ledson and Greg Cunningham on the sidelines, who will both undergo late fitness checks.
Declan Rudd and Patrick Bauer remain out, and are unlikely to play before the end of the season.
Nathan Jones could have integral centre-back Tom Lockyer available, after he returned to training following an ankle injury.
Sonny Bradley and Dan Potts are both expected to miss out with thigh and head injuries respectively.
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Predicted lineups
Preston (4-2-3-1):
Iversen; Van den Berg, Huntington, Storey, Hughes; Molumby; Whiteman; Sinclair, Johnson, Barkhuizen; Evans.
Luton (3-5-2):
Sluga; Naismith, Rea, Pearson; Bree, Mpanzu, Dewsbury-Hall, Tunnicliffe, Clark; Adebayo, Collins.
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Ones to watch
Scott Sinclair
31-year-old Scott Sinclair has been in the game for what feels like forever, and has unsurprisingly been a stand-out performer for Alex Neil's side this season. 10 years on from firing Swansea City to the Premier League, the winger has scored nine goals in 32 appearances this season.
Preston will need him at his best to get past a rigid Hatters backline on Saturday.
Elijah Adebayo
Elijah Adebayo is enjoying his breakthrough season in this campaign, as opposed to Sinclair all those years ago. The 23-year-old joined Town from Walsall in January and hasn't looked back, with three goals and an assist in just five starts for his new club.
Nathan Jones will hope his new star man can bag his first goal away from home to fire his side to victory at Deepdale.
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Previous meetings
The reverse fixture saw Jones' men run out 3-0 winners at Kenilworth Road in front of 1,000 spectators.
James Collins was the star of the show that day, with his first Championship hat-trick sealing an emphatic victory.
The last game between the two at Deepdale saw the Lilywhites take home the three points.
A late Jayden Stockley goal claimed a 2-1 win after Paul Gallagher had put the hosts ahead and Collins had equalised for the away side.
The Hatters have a poor record in Lancashire, with their last win at Deepdale coming in January 1972.
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Where to watch
The game kicks off at 3pm on Saturday March 20.
Match passes for iFollow coverage can be purchased from either club's website for £10 for customers in the UK and Ireland.
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What the managers have said
Alex Neil was complimentary to his opposing manager when talking to Preston's official website.
He said: “Nathan has done a really good job there. They are tough opponents. The game down there was a low point for us this season in terms of how we performed and they were very good.
“If we can go and try and get a good result out of this game, it means we can go into those two weeks with optimism and try and look forward to the remaining eight games.”
Town's assistant manager Mick Harford spoke to the press on Thursday, and outlined their aims for the end of the season.
He said: "It would be a massive achievement if we get to 50 points before the international break.
“Our aim is to win as many games as we can, to get as many points on the board as we can, aim high and who knows where it will take us.
“If we can get to 50 points then we can play with that bit of freedom that certain teams do in those times, and who knows what can happen?”