The visitors will also be looking to end a poor run of form after failing to win any of their last three matches in the third tier.
Match preview
Northampton are languishing in 20th place in the League One table after winning two, drawing two and losing five of their nine matches.
Since claiming their most recent league win over Huddersfield Town, the Cobblers have gone on to lose three consecutive league matches, including back-to-back home games against Mansfield Town and Bolton Wanderers.
Northampton then experienced a forgettable trip to Wales in their recent clash against Wrexham, with Cameron McGeehan's effort proving to be a mere consolation in a heavy 4-1 defeat.
While they may be struggling in the league, they did at least build some confidence with a 2-0 away win in their EFL Trophy meeting with League Two Notts County.
The Cobblers will now return to Sixfields, where they have gone four games without a win (D1, L3) since beating Exeter City in their first home game of the season.
Leyton Orient are currently sitting level on eight points with Northampton after winning two, drawing two and losing six of their 10 league matches.
The 19th-placed side have taken just two points from four league games since cruising to a 4-1 away win over Stockport County on September 21.
The O's played out back-to-back draws with Peterborough United and Wrexham, before they fell to consecutive defeats Exeter City and Lincoln City.
Leyton Orient were unable to return to winning ways in their recent EFL Trophy outing against Colchester United, but they did prevail in the penalty shootout to clinch a useful bonus point after the contest finished 1-1 in regulation time.
The O's will now turn their focus to Saturday's away trip, and while they have failed to win their previous three away games against Northampton, they may be able to take confidence from the 4-3 home win they recorded in their most recent head-to-head meeting in February.
Northampton Town League One form:
D
L
W
L
L
L
Northampton Town form (all competitions):
L
W
L
L
L
W
Leyton Orient League One form:
W
W
D
D
L
L
Leyton Orient form (all competitions):
W
D
D
L
L
W
Team News
Northampton are having to cope with a lengthy injury list which includes Patrick Brough, Ali Koiki, Luke Mbete, Harvey Lintott and Callum Morton.
Aaron McGowan is sidelined after he picked up a calf injury against Wrexham, while fellow defender Jordan Willis will also miss the home game through injury.
With Jon Brady coping with several defensive absentees, he could select a back four of Akinwale Odimayo, Jack Baldwin, Jon Guthrie and Nesta Guinness-Walker.
As for the visitors, they are expected to make several changes to the side that started the EFL Trophy win over Colchester.
Tom James, Omar Beckles and Jack Currie are all likely to be recalled to the Leyton Orient backline for Saturday's away trip.
Dan Agyei, Ollie O'Neill and Tottenham Hotspur loanee Jamie Donley are also among those who could come back into the starting lineup.
Northampton Town possible starting lineup:
Burge; Odimayo, Baldwin, Gutherie, Guinness-Walker; Sowerby, McGeehan; Hoskins, Roberts, Fosu; Eaves
Leyton Orient possible starting lineup:
Hemming; James, Beckles, Simpson, Currie; O'Neill, Brown, Ball, Donley, Agyei; Kelman
We say: Northampton Town 1-1 Leyton Orient
Having claimed just two league wins apiece, Northampton and Leyton Orient will both be desperate to claim all three points in Saturday's contest.