The Cumbrians have lost each of their last five matches, while Pompey have dropped just two points in their previous four outings.
Match preview
Carlisle are still searching for their first win since New Year's Day after losing five consecutive matches, including their most recent fixture against Leyton Orient.
The Cumbrians took the lead through Josh Vela in the 21st minute, before a Shaq Forde brace and a Ruel Sotiriou strike turned the game in Leyton Orient's favour.
While Sean Maguire dispatched a stoppage-time penalty, it proved too little too late as Carlisle fell to their eighth defeat in their last nine away league matches (D1).
With 11 points separating them from safety, Paul Simpson's side have significant work to do if they are to avoid an immediate return to League Two.
Having conceded 14 goals across their last five matches, Carlisle will need to tighten up defensively if they are to trouble the league leaders on Saturday.
In contrast to their hosts, Portsmouth will head into the weekend in a confident mood after cruising to a 4-1 victory over Northampton Town last weekend.
Conor Ogilvie and Paddy Lane grabbed a goal apiece to give Pompey a two-goal lead at the break, but John Mousinho's side were dealt a blow in the second half when Tom McIntyre was shown a straight red card on his debut.
Despite being reduced to ten-man, Lane and Callum Lang added to Portsmouth's advantage, before Norhampton's Marc Leonard netted a late consolation in Pompey's third victory in four matches.
Having won 18, drawn nine and lost four of their 31 matches, Portsmouth currently enjoy a four-point lead over Derby County and a five-point cushion to third-placed Bolton Wanderers.
Impressively, Pompey have managed to avoid defeat in their last eight competitive meetings with Carlisle (W4, D4) since losing 4-2 in August 2012.
Carlisle United League One form:
W
L
L
L
L
L
Portsmouth League One form:
L
L
W
W
D
W
Team News
Carlisle are expected to be without the services of Callum Guy, Georgie Kelly and Josh Kayode, who are all recovering from their respective injuries.
Full-back Josh Emmanuel is closing in on a return to fitness, but it remains to be seen whether he will be ready for the weekend.
Simpson is hoping to have Jack Robinson and Jack Diamond available after the pair picked up knocks in the defeat to Leyton Orient.
While Pompey won their appeal to overturn McIntyre's red card, the January signing has been ruled out for the rest of the season with a fractured ankle.
Joe Morrell and Terry Devlin have also picked up season-ending injuries to add to an absentee list that features Zach Swanson, Regan Poole, Tino Anjorin and Alex Robertson.
In more positive news, Australia international Kusini Yengi is expected to be on the bench after returning from the Asian Cup in Qatar.
Owen Moxon, who completed a move from Carlisle last month, is set to feature among the substitutes against his former club.
Carlisle United possible starting lineup:
Lewis; Back, Barclay, Lavelle, Mellish, Robinson; Gibson, Neal, Vela; Armstrong, Diamond
Portsmouth possible starting lineup:
Norris; Rafferty, Shaughnessy, Raggett, Ogilvie; Lowery, Pack; Lane, Lang, Peart-Harris; Bishop