Meanwhile, newly-promoted Port Vale are unbeaten in their last three outings in all competitions.
Match preview
These two sides are only separated by goal difference in the table, but Cambridge come into this clash in spiralling league form.
It has been a drastic downturn in results for the U's with a victory at basement boys Morecambe the only exception on their dreadful run.
Mark Bonner's side have now lost their last four in the league, including the 2-0 defeat to Sheffield Wednesday last weekend courtesy of a Lee Gregory brace.
However, they did defeat Ipswich Town 1-0 in the EFL Trophy in midweek, due to a late Lewis Simper strike. The 21-year-old's first goal of the season was enough to give Bonner's side the victory and avoid five straight defeats in all competitions.
On an evening when his men bowed out of the EFL Trophy despite picking up six points in the group stages, Bonner will see the return to winning ways as a building block heading into some crucial encounters in the league.
The victory over Ipswich could be the result the U's need to get back on track in the league and end this barren run.
Meanwhile, the visitors' inconsistency means they are still looking both up the table and over their shoulder as they have become stranded in mid-table following a mix of wins, draws and losses.
They currently sit one place above their opponents on Saturday due to goal difference, however, the Valiants do have a game in hand.
Darrell Clarke's side followed up their brilliant away win at Derby County with a 2-2 draw with fellow promoted side Forest Green Rovers last time out in the league.
A late Ellis Harrison penalty completed Port Vale's comeback from two goals down, after Myles Peart-Harris and Baily Cargill had given Rovers the lead.
Mipo Odubeko pulled a goal back for The Valiants before Harrison slotted away his seventh goal of the season from 12 yards out.
That goal puts the Welshman in a tie for fourth in the goalscoring charts, as he has now scored exactly half of Port Vale's goals in League One this campaign.
The EFL Trophy victory over Wolverhampton Wanderers' Under-21s in midweek means that Port Vale are undefeated in their last three outings in all competitions, and they will be fancying their chances against an out-of-sorts Cambridge side here.
The win sees the Vale secure a home tie in the last 32, with ties to take place in the week commencing November 21.
Cambridge United League One form:
L
W
L
L
L
L
Cambridge United form (all competitions):
W
L
L
L
L
W
Port Vale League One form:
D
W
L
L
W
D
Port Vale form (all competitions):
W
L
L
W
D
W
Team News
The hosts could still be without Adam May after the midfielder was ruled out of last weekend's defeat to Sheffield Wednesday with a knee injury.
Goalkeeper Will Mannion missed the defeats against Bristol Rovers and Wednesday with a knee injury but he returned in midweek against Ipswich, so he could retain his place here.
Summer signing Brandon Haunstrup has missed the last eight league games and is not expected to feature.
Harrison Dunk has not played for the U's since the defeat to Derby County at the start of the month due to a knee problem, and is touch-and-go for the match on Saturday.
Meanwhile, Port Vale will remain without Belgian midfielder Funso Ojo and striker Jamie Proctor as they continue to recover from hamstring and hip injuries respectively.
Rory Holden returned to action against Wolves' Under-21s on Tuesday evening, and Harry Charsley could be close to coming back from injury.
Cambridge United possible starting lineup:
Mannion; Jones, Taylor, Williams; Tracey, Digby, Knibbs, Simper, Brophy; Ironside, Smith
Port Vale possible starting lineup:
Stevens; Smith, Forrester, Jones; Massey, Garrity, Politic, Conlon, McCarron; Wilson, Harrison
We say: Cambridge United 0-2 Port Vale
Port Vale are unbeaten in their last three, and although they may not have the most potent attack, they face a Cambridge side who have been generous in giving up goals.