The U's have not won at home in League One in their last five outings, while Stanley are looking to secure their first three points in the league since October 1.
Match preview
Cambridge scraped past National League North side Curzon Ashton on penalties last time out, to book their place in the FA Cup second round.
The two sides could not be split over 180 minutes of action, but it was the League One outfit that remained composed from the spot.
Joe Ironside, Jack Lankester, Harvey Knibbs and Paul Digby all found the target from 12 yards for Cambridge, to set up a home tie with League Two club Grimsby Town on November 26.
Mark Bonner's side have struggled in league action this season, as they currently sit 18th in the table, six points clear of the relegation places.
The Yellows have only scored 18 goals in their opening 18 games, and their last result in the league was a respectable 0-0 draw with seventh-placed Bolton Wanderers.
Bonner will fancy his team's chances on Saturday, coming up against an Accrington Stanley side that are below them in the table, and have only won two games on their travels this season.
However, Cambridge have not won at the Abbey Stadium in the league since they beat Lincoln City 2-0 on September 3.
Meanwhile, Accrington Stanley have only picked up one point in their last seven league games leaving them in 20th place in League One, just three points clear of the relegation places.
The Reds lost narrowly to promotion-chasing Sheffield Wednesday last weekend, courtesy of a first-half strike from Alex Mighten.
Stanley's last victory in the league was a 3-0 win over Morecambe back at the start of October, and the early indications are that John Coleman's side could be involved in a relegation battle in the third tier this season.
Coleman will be hoping that his team can build on their last victory away from home, which was a 4-1 victory against Crawley Town in the FA Cup first round.
Shaun Whalley celebrated his first senior hat-trick to fire Stanley into the second round, where the Reds will host Barnet, but league results will be the priority for Coleman and his staff.
Cambridge United League One form:
L
L
L
W
L
D
Cambridge United form (all competitions):
L
W
L
D
D
W
Accrington Stanley League One form:
L
L
L
L
D
L
Accrington Stanley form (all competitions):
L
L
L
D
W
L
Team News
Following the stalemate against Bolton Wanderers three days prior, Mark Bonner rotated his side and made five changes against Curzon Ashton, so he could shuffle the pack once again here.
Greg Taylor, Ben Worman, Saikou Janneh, Sam Smith and Shilow Tracey all returned to proceedings against the non-league outfit, while academy starlet George Scales made the bench.
As for the visitors, Sean McConville and Joe Pritchard both had to be substituted early against Sheffield Wednesday due to potential injury concerns.
Seamus Conneely replaced top scorer McConville, while Rosaire Longelo-Mbule came on for Pritchard at the interval, so they could both be in the starting XI on Saturday.
Ryan Astley missed the clash against the Owls, and he is expected to miss out again here due to injury.
Cambridge United possible starting lineup:
Mannion; Williams, Okedina, Jones, Dunk; Simper, Digby; Knibbs, Smith, Brophy; Ironside
Accrington Stanley possible starting lineup:
Savin; Rodgers, Fernandes, Tharme; Clark, Martin, Hamilton, Conneely, Longelo-Mbule; Whalley, Leigh
We say: Cambridge United 1-0 Accrington Stanley
We are not expecting this to be an open and entertaining affair given the fact that both sides have only found the net 18 times this season.