Meanwhile, newly-promoted Carlisle will be keen to build on their draw with Fleetwood Town last weekend as they bid to establish themselves in the third tier.
Match preview
Ahead of the new campaign, Oxford were regarded as one of the favourites for promotion, Liam Manning fancied to spearhead a much-improved season.
However, a 2-0 defeat at Cambridge United represented a poor start, Oxford conceding twice in the opening 28 minutes.
An EFL Cup tie at Bristol City gave Manning's side a chance to go someway to redeeming themselves, yet they were blown away by their Championship hosts.
Succumbing to a 5-1 reverse at Ashton Gate has left confidence considerably low in the build-up to this fixture, one which will already be deemed to be a must-not-lose.
While Oxford have bought extremely well this summer, they are devoid of momentum as well as togetherness, and they are in desperate need of a response at the Kassam Stadium.
As for Carlisle, the 2023-24 campaign is all about trying to consolidate their position in the third tier having upset the applecart in last season's League Two playoffs.
Posting a 1-1 draw with Fleetwood Town last Saturday was a solid-enough start to their schedule, Paul Simpson wanting to build on that result on Saturday.
Nevertheless, there was disappointment as Carlisle lost 1-0 at Harrogate Town in the EFL Cup, even if Simpson will not be too against a couple of fewer games on the calendar.
Given some of the names that have arrived at Brunton Park over the summer, the Cumbrians look in good shape to avoid a relegation battle, yet it is games such as this one where they need to showcase their qualities.
Oxford United League One form:
Oxford United form (all competitions):
Carlisle United League One form:
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Carlisle United form (all competitions):
Team News
Although Manning only made four outfield changes to his Oxford XI for the game with Bristol City, the players who dropped out should return for this fixture.
Fin Stevens did his hopes of a first league start at right-back no harm by providing the assist for Billy Bodin's goal on Wednesday.
Max Woltman, who has been signed from Liverpool, will be considered for a start in attack ahead of Mark Harris.
Joe Garner and Sean Maguire are each pushing for starting roles in the Carlisle attack ahead of new arrival Luke Plange.
Owen Moxon will feature if he can shake off a dead leg, while Paul Huntington and Fin Back should return to the side after being rested in midweek.
Oxford United possible starting lineup:
Beadle; Long, Moore, Thorniley, Brown; McEachran, Brannagan; Goodrham, Rodrigues, Browne; Harris
Carlisle United possible starting lineup:
Holy; Levelle, Huntington, Mellish; Back, McCalmont, Guy, Moxon, Armer; Gibson, Garner
We say: Oxford United 2-1 Carlisle United
Manning will feel that he and his Oxford side are under pressure to deliver in this game, whereas Carlisle can play with a certain level of freedom. Despite those contrasting mentalities, we are backing Oxford to edge this fixture, potentially with a goal in the closing stages.