The game will be the Blues’ second trip to Brisbane Road this season, with a 4-0 victory recorded against the O’s back in August.
However, there’ll be plenty of changes to the side that easily brushed aside Richie Wellens’ side that memorable day. There’ll also be wholesale changes from Sunday’s loss at the Proact Stadium, with head coach Mousinho having one eye on Saturday’s important league game against Charlton.
A growing injury list, however, means Pompey’s options are starting to stretch, especially if the boss wants to keep first-team regulars fresh for the challenge the Addicks will pose at the weekend.
So what sort of team do we think will take to the pitch at Brisbane Road tonight (kick-off 7pm)? Well, here’s how we think the Blues will line up.
5. Centre-back 2: Ryley Towler
The centre-back has played just five games all season to date, with just two of those coming in the league. Towler's last outing was the 5-1 hammering of Gillingham in the Blues' previous EFL Trophy run out. He'll need to dust down any cobwebs tonight as Conor Shaughnessy is given the night off ahead of the Charlton game. Photo: Jason Brown
6. Left-back: Denver Hume
Could this be the night that Pompey's forgotten man make his Blues comeback? The former Sunderland man hasn't been used in any competition this season, with his last appearance coming in a July pre-season friendly against Bognor. However, with Connor Ogilvie out injured and Jack Sparkes most likely needing a rest ahead of Charlton, Hume could be the man to step up. He was spotted sitting on the Pompey bench against Chesterfield on Saturday as he travelled with the squad. He was clearly Pompey's 21st man on Sunday. Next stop - a rare appearance in the EFL Trophy. Photo: Jason Brown
7. Central midfield 1: Ben Stevenson
The solid and dependable midfielder walks into tonight's side as John Mousinho wraps Joe Morrell and Alex Robertson up in cotton wool ahead of the Charlton game. Photo: Jason Brown
8. Central midfield 2: Terry Devlin
John Mousinho will loathe to use the Irishman against Leyton Orient after starting Pompey's past two games. But with Marlon Pack, Tom Lowery and Tino Anjorin all out injured and Joe Morrell and Alex Robertson needed for Saturday, his options are limited. The game will give Devlin another good opportunity to get more experience under his belt, though. Photo: Jason Brown