Meanwhile, the hosts have little to play for after their relegation was confirmed following their recent defeat to Bolton Wanderers.
Match preview
Port Vale will be playing their football in the fourth tier next season after their two-year stay in League One was ended by a 2-0 defeat to Bolton last weekend.
Aaron Collins and Cameron Jerome got on the scoresheet to condemn the Valiants to a fourth consecutive defeat, leaving them stranded in 23rd place with just 40 points from 45 matches.
Port Vale boss Darren Moore has only been able to win two of his 16 games since being appointed on a five-and-a-year deal in February.
Despite the club's relegation, Port Vale co-owner Carol Shanahan has confirmed Moore will remain in his post to lead the rebuild at Vale Park.
Before they focus on preparations for next term, the Valiants will look to end a six-game winless run in their final match of the season.
Cambridge could still join Port Vale in League Two after they missed the chance to guarantee safety in Tuesday's home meeting with Wycombe Wanderers.
The U's appeared to be heading towards a precious win when Gassan Ahadme opened the scoring in the 71st minute, only for Luke Leahy to level from the spot to ensure the spoils were shared, leaving Cambridge without a win in five matches.
With three points separating them from 21st-placed Cheltenham Town, the U's will stay up if they collect a point in their final outing of the League One season.
However, if they lose to Port Vale, Garry Monk's side will be relegated if Cheltenham win and Burton Albion beat Fleetwood Town.
A win and a Burton draw could also see Cambridge relegated if they lose by three goals or more in Saturday's away fixture.
The visitors may be able to take confidence from the fact they have won both of their last two away matches against Port Vale.
Port Vale League One form:
L
D
L
L
L
L
Cambridge United League One form:
W
L
D
L
L
D
Team News
Port Vale is expected to be without the services of Mitch Clark, Dan Gore, James Wilson and James Plant.
Conor Grant is a doubt for Saturday's contest after he was forced off in the first half against Bolton due to an injury issue.
Grant is likely to be replaced by Jake Sherrock, while there could also be starting spots for Baylee Dipepa and Ryan Loft.
As for the visitors, they may be unable to call upon Jack Stevens, George Thomas and Mamadou Jobe, while Zeno Ibsen Rossi is a doubt following his absence in midweek due to injury.
Cambridge will hope to have Danny Andrew and Ryan Bennett after the pair missed Tuesday's clash with Port Vale through illness.
Harrison Dunk, who has been out of action since September, has played his final game for the club following the announcement that he will leave when his contract expires at the end of June.
Port Vale possible starting lineup:
Ripley; Debrah, Smith, Iacovitti; Sang, Garrity, Ojo, Sherrock; Chislett; Dipepa, Loft
Cambridge United possible starting lineup:
Mannion; R Bennett, Andrew, Gibbons; L Bennett, Digby, Cousins, Brophy; Kachunga; Ahadme, Bonne