The Tykes are sixth in the table on 47 points and are well placed for a tilt at the playoffs in 2022-23, or possibly more, depending on how their form goes.
Cambridge are in 23rd place, and are deep in the relegation mire ahead of the trip to Yorkshire on Saturday.
Match preview
Michael Duff has had a respectable first season in charge of Barnsley following his move to the Tykes in the summer, after he led Cheltenham Town to promotion to the third tier in 2021-22.
Duff also has a great record against Cambridge, having lost only one of his last seven matches as a manager against Saturday's opponents.
Whilst the Yorkshiremen may not be taking League One by storm as they had done in previous seasons, the Northern Irishman has the team currently positioned in sixth place, and the Tykes will fancy their chances of at least finishing in the playoff places at the end of the season.
Barnsley have the chance to consolidate their position in the playoff places with a win over struggling Cambridge at Oakwell on Saturday. Depending on other results, victory over the U's could take the Tykes to within three points of Derby County and Bolton Wanderers, who are fourth and fifth respectively, and also to within five points of Ipswich Town in third.
More importantly, the South Yorkshire side can stretch their lead over Peterborough United in seventh to six points with a win over Cambridge, should Posh fail to win themselves.
Barnsley are currently on a three-game unbeaten run following a 1-1 draw with Portsmouth at Fratton Park last weekend, and they will be hoping to make it three wins from their last four league games, by gaining another maximum-point haul against United.
Barnsley are 12th in League One for goals scored per match with 1.3, so the team's top scorer Devante Cole will hope to increase his league tally of seven goals in order to move the Tykes up both the goals scored table and the League One table, starting on Saturday.
Michael Duff's side have also gone eight games without recording a clean sheet, so the team's defence but particularly the three central defenders, captain Mads Juel Andersen, Liam Kitching and the man who scored a late equaliser against Pompey, Bobby Thomas, will be hoping to rectify this and record a shutout against Cambridge.
Mark Bonner's Cambridge United are having a wretched season - the U's are 23rd in the table and are winless in their last six games in all competitions, since a 2-1 win at home to Shrewsbury Town on Boxing Day, losing four of those games.
Cambridge will be hoping to kickstart their season with victory at Oakwell on Saturday, but to do so, they will have to turn around their awful away form of no wins on their travels in seven matches.
Three points on Saturday could take United out of the relegation zone, but this is dependent on the sides above them dropping points.
If the Amber Army are to survive, they will need more goals from their wingers Liam Bennett and James Brophy, in order to ease the goalscoring burden on the forwards, Harvey Knibbs, Joe Ironside and top scorer Sam Smith, whose goal tallies of five and six respectively would be fine if they were matched elsewhere in the team.
Cambridge also have the fourth-worst defensive record in the league this season, so their back three of Michael Morrison, Ryan Bennett and Lloyd Jones will need to tighten up if the team are to escape from danger.
The U's defence will hope to use Saturday's trip to Yorkshire as a starting point for an improvement in the goals against column, although they were well beaten 3-0 in the reverse fixture.
Barnsley League One form:
W
L
L
W
W
D
Barnsley form (all competitions):
L
L
L
W
W
D
Cambridge United League One form:
L
L
L
L
D
D
Team News
Neither Barnsley nor Cambridge have any fresh injuries ahead of Saturday, with the Tykes' Luke Thomas and United's Adam May being long-term absentees with lower leg and cruciate ligament injuries, respectively.
Michael Duff is likely to set the hosts up in their usual 3-5-2 formation, with a midfield trio of Luca Connell, Herbie Kane and Adam Phillips being charged with both protecting the back three and supporting the front two, Max Watters and Cole.
The side's wing-backs Nicky Cadden and Jordan Williams will also fulfil attacking and defensive duties, whilst simultaneously providing the Tykes' width.
Cambridge United will also utilise a back three on Saturday, but their 3-4-1-2 system will mean that Harvey Knibbs will play as a true number 10 and have license to support Joe Ironside and Sam Smith upfront.
Ben Worman and Paul Digby will form the Yellows' engine room from central midfield, whilst Dimitar Mitov will once again be between the sticks for the visitors.
Barnsley possible starting lineup:
Collins; Williams, Andersen, Kitching, Thomas, Cadden; Connell, Phillips, Kane; Watters, Cole
Cambridge United possible starting lineup:
Mitov; Morrison, Bennett, Jones; Bennett, Digby, McGrandles, Brophy; Knibbs; Ironside, Smith
We say: Barnsley 2-1 Cambridge United
A game against promotion-chasing Barnsley at Oakwell will surely be too much for a struggling Cambridge side to cope with. Barnsley's clean sheet-shy defence will give United hope, but possibly not enough for them to get a result.