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.
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.
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.
