Pompey, meanwhile, will have the chance to record a second straight victory after beating Burton Albion in midweek.
Match preview
After going five games without a win, Northampton have turned the tide in recent weeks to embark on a run of three successive league victories.
They claimed home wins over Burton Albion and Cambridge United, before they made the midweek trip to Bloomfield Road for a tricky meeting with Blackpool.
Despite seeing Jordan Rhodes cancel out Kieron Bowie's opener, the Cobblers still returned home with all three points thanks to Sam Hoskins's 11th goal of the season.
From finishing October in 20th place and level on points with the drop zone, Northampton are now in 13th position with seven points separating them from the bottom four.
Although they face a tough test this weekend, Northampton will look to draw inspiration from their most meeting with Portsmouth, which saw them run out 4-1 winners in March 2021.
Portsmouth enjoyed a 27-game unbeaten league run before their impressive run of form was brought to a disappointing end with a heavy 4-0 defeat to Blackpool last weekend.
After suffering their first league defeat in eight months, Pompey quickly picked themselves up to return to winning ways in their midweek away fixture against Burton Albion.
Colby Bishop opened the scoring from the penalty spot, before Manchester City loanee Alex Robertson scored his first Pompey goal to wrap up the club's 11th league win of the season.
As a result, John Mousinho's side are sitting in second place and level on 39 points with league leaders Bolton Wanderers, who they will face on December 11.
Before they can prepare for that top-of-the-table clash, Pompey will have the chance to extend their unbeaten league run to 15 matches.
Northampton Town League One form:
D
L
L
W
W
W
Northampton Town form (all competitions):
L
L
W
L
W
W
Portsmouth League One form:
W
D
W
D
L
W
Portsmouth form (all competitions):
W
L
W
D
L
W
Advert - content below:
Team News
The Cobblers will be without left-back Ali Koiki, who is set for a spell on the sidelines after recently picking up an injury against MK Dons in the EFL Trophy.
Northampton boss Jon Brady has revealed he will make a late decision on the availability of Jon Guthrie and Patrick Brough.
If neither of the pair are able to take their place in the squad, Brady could decide to select the same lineup that started against Blackpool in midweek.
As for the visitors, their injury list features Regan Poole, Conor Ogilvie, Tom Lowery, Anthony Scully and Faustino Anjorin due to injury.
They are also unable to call upon Wales international Joe Morrell, who is set to serve the second and final match of a two-game suspension.
Bishop, who is Pompey's top scorer this season, is also expected to miss out after being forced off at half time against Burton with an ankle problem.
Northampton Town possible starting lineup:
Thompson; McGowan, Willis, Sherring, Odimayo; McWilliams, Leonard, Sowerby; Pinnock, Hoskins, Bowie
Portsmouth possible starting lineup:
Norris; Rafferty, Raggett, Shaughnessy, Sparkes; Robertson, Pack; Lane, Kamara, Martin; Yengi