A 2-1 win at Crewe Alexandra on January 18 took Russell Slade's side top of the table, but defeats from each of their last three games have seen Orient's top-two credentials come into question.
Orient head to Deepdale with a one-place and five-point lead over their opponents, although fourth-placed Preston still have the luxury of a game in hand.
A single Joe Garner goal was enough to give the Lancashire side victory in the reverse fixture at Brisbane Road in November, and a win this time around would seal a first league double over the London club since 1996.
League leaders Brentford return to action - having not played since February 1 - with a trip to struggling Crewe.
Mark Warburton's side have not tasted defeat in 18 league outings and sit two points clear of nearest rivals Wolves, who take on relegation-threatened Notts County.
Elsewhere at the top, fifth-placed Rotherham United will look for a fifth win in six games when they take on bottom-of-the-table Stevenage.
A late Britt Assombalonga header was enough to secure a 2-1 win for sixth-placed Peterborough United away to Leyton Orient last week, a result that kept his side's push for the play-offs on track.
The 21-year old has netted 16 league goals so far this season, including five in his last four appearances, and will undoubtedly worry Walsall boss Dean Smith, who will demand a reaction from his men when they travel to London Road on Friday.
Walsall were thumped 3-0 at home to MK Dons last weekend, their first defeat since Boxing Day, leaving them two points adrift of their opponents in seventh place.
Friday's other match sees Swindon Town, who have play-off aspirations of their own, entertain Colchester United.
At the other end, Shrewsbury Town will attempt to halt a rotten run of five defeats in their last six when they host Port Vale in Saturday's early kick-off.
Much has been made in the national media of Bristol City's decision to support safe standing this week, but Steve Cotterill's men are still looking nervously over their shoulder when it comes to matters on the pitch, despite a vital win over Leyton Orient in midweek.
They face fellow strugglers Tranmere Rovers at Ashton Gate, with both teams sitting just one point off the relegation zone, level on points with Crawley Town, who host Carlisle United.
Elsewhere Coventry City entertain Bradford City, while Oldham Athletic travel to MK Dons.
