The visitors will move two points clear of the bottom four with a victory in Staffordshire, while the hosts have already secured their place in the third tier for another season.
Match preview
Sitting eight points clear of the drop zone with two matches remaining, Burton Albion will be playing League One football next term, despite winning just one of their last four matches.
The Brewers were beaten 1-0 at Plymouth Argyle on Saturday, although the visitors could - and probably should - have suffered a heavier defeat after facing 22 shots and managing a solitary attempt on target.
Nevertheless, Burton will be confident of bouncing back when they return to the Pirelli Stadium on Wednesday, as Dino Maamria's men have enjoyed plenty of success on home soil in recent times.
In fact, Burton Albion have lost just one of their last eight home games in League One, picking up five wins along the way, with only two defeats coming in their previous 15 home league outings.
Although the Brewers possess the second-worst defensive record in the division, having conceded 79 goals in 44 matches this season, their impressive home form makes them dangerous opponents for struggling Cambridge United.
The U's looked destined for relegation when they ended a run of one victory in 15 league outings between December and March, suffering 11 defeats in the process.
However, Cambridge have given themselves a fighting chance of beating the drop thanks to a series of positive results of late, with four wins coming in their last seven matches.
After ending a six-game winless run with back-to-back victories over Port Vale and Fleetwood Town, Mark Bonner's men held Bolton Wanderers to a draw before defeating Peterborough United.
Defeats to Wycombe Wanderers and Plymouth Argyle followed that four-match unbeaten streak, but Cambridge managed to return to winning ways last time out, sealing a crucial 2-1 victory at relegation rivals Accrington Stanley.
Saturday's triumph saw Cambridge United move two points clear of Accrington Stanley and one point from safety with a game in hand, so Bonner's men will carry plenty of momentum in Wednesday's pivotal showdown.
Burton Albion League One form:
L
W
D
L
W
L
Cambridge United League One form:
W
D
W
L
L
W
Team News
Burton Albion right-back Tom Hamer looks set to remain on the sidelines after missing the past nine matches through injury.
Striker Sam Winnall is also likely to be absent from Wednesday's matchday squad, having made a solitary substitute appearance since picking up an injury back in February.
Jasper Moon, Sam Hughes and John Brayford are expected to continue in defence, while Josh Walker should lead the line for the hosts.
On the flip side, Cambridge United will be without Adam May for the remainder of the campaign after the midfielder sustained an ACL injury earlier this season.
Harrison Dunk will retain his place in the visitors' starting XI after scoring last time out, while Liam Bennett is expected to occupy the other full-back spot.
Sam Smith will continue to lead the line for Cambridge, with Mark Bonner likely to call upon Joe Ironside from the bench.
Burton Albion possible starting lineup:
MacGillivray; Brayford, Hughes, Moon; Oshilaja, Shaughnessy, Powell, Ashworth; Latty-Fairweather, Helm; Walker
Cambridge United possible starting lineup:
Mitov; Bennet, Bennet, Morrison, Dunk; McGrandles, Digby; Brophy, Lankester, Knibbs; Smith
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