Both clubs are flirting with a possible relegation battle, and Cambridge could be leapfrogged by their fifth-bottom opponents if beaten this weekend.
Match preview
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Cambridge have not won since September 4 — a 1-0 triumph over Reading — and they continue to slide down the table as results deteriorate.
Three of their four victories have been at the Abbey, but the last time they secured maximum points in front of their fans was at the start of the previous month against the Royals.
Mark Bonner's team do not score enough on their turf, underscored by eight strikes in as many games and the same number conceded, with 50% coming in the 4-0 loss against third-placed Barnsley in early October.
With five points separating the home side from Wigan Athletic in the bottom four, Cambridge must find their feet to avoid sliding down the table.
Further dropped points would suggest the problems run deeper for Bonner's men, but it remains to be seen if Saturday's game is the turning point for the out-of-form side.
As for Carlisle, their three-point advantage over 21st-placed Wigan was maintained with a 2-1 win over Burton Albion on Tuesday, thus keeping them away from the relegation spots.
The Cumbrians were in danger of falling into the bottom four after consecutive defeats against Leyton Orient and table-topping Portsmouth, emphasising the importance of this week's win.
Travelling to Cambridge represents a different challenge for a side that have picked up five points from a possible 21 on their away trips, suggesting disappointment could be in the offing this weekend.
They did score three times at fourth-placed Bolton Wanderers on October 7, defeating the playoff hopefuls 3-1 at the Toughsheet Community Stadium, offering hope that impressive performances and results are in this team's locker.
Paul Simpson guided Carlisle to League One promotion via the playoffs a few months back, but the jury is still out on their capabilities at this level.
Cambridge United League One form:
D
L
L
D
L
D
Cambridge United form (all competitions):
L
L
D
L
L
D
Carlisle United League One form:
L
D
W
L
L
W
Carlisle United form (all competitions):
D
W
L
L
L
W
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Team News
Cambridge came out unscathed after their creditable draw with league leaders Portsmouth this week, and minimal changes are expected.
However, Fejiri Okenabirhie, whose five league goals outdoes his colleagues, could return to the team on Saturday.
Alfie McCalmont was forced off with an injury last weekend, and the Carlisle man's non-participation in Tuesday's win at Burton suggests he remains in the wars.
With McCalmont potentially out, Simpson could stick to the same 4-2-3-1, leaning on most of the starters from the 2-1 triumph.
Cambridge United possible starting lineup:
Stephens; Bennett, Bennett, Morrison, Andrew; Digby, Thomas; Brophy, May, Ahadme; Okenabirhie
Carlisle United possible starting lineup:
Holy; Back, Lavelle, Mellish, Armer; Guy, Moxon; Maguire, Butterworth, Gibson; Garner
We say: Cambridge United 1-1 Carlisle United
A draw could be on the cards in Cambridge, as the hosts have not pulled up trees in recent home games, while Carlisle have claimed one victory in their last five away fixtures.