The two sides will be looking for a positive response after they both suffered defeats in the FA Cup third round at the weekend.
Match preview
Wimbledon saw their FA Cup journey come to an end in Saturday's home meeting with Championship high-flyers Ipswich Town.
Jake Reeves dispatched a 17th-minute penalty to pull Wimbledon level following a Josh Davison own goal, before Axel Tuanzebe found the net to give Ipswich a narrow half-time lead.
The League Two side kept the Tractor Boys within touching distance until Jack Taylor found the net in the 90th minute to condemn Johnnie Jackson's side to a 3-1 loss, representing their second defeat in three home games.
While they face another tough test on Tuesday, Wimbledon can take confidence from the fact they beat a League One promotion contender in the previous round, producing a free-scoring display to claim a 5-2 away win over Portsmouth.
They will enter the midweek contest with hopes of reaching the quarter-final stage for the first time since 2020-21 when their journey was ultimately ended by a 3-1 defeat to Oxford.
Although the U's will be hoping to experience similar success against Wimbledon on Tuesday, they will have to pick themselves up from a heavy 6-2 loss to Coventry City in the FA Cup.
Mark Harris and Tyler Goodrham both got on the scoresheet in Saturday's cup tie, but their efforts proved fruitless in what proved to be a disappointing result for Des Buckingham's side.
The Oxford boss will be frustrated by his team's lack of consistency, having seen his side win three, lose four and draw one of their last eight matches in all competitions.
They have also won just one of their last five competitive away games, although they have claimed victories in both of their away matches in the EFL Trophy this season, including a narrow 1-0 win in the previous round against Forest Green Rovers.
Like Wimbledon, the U's are also aiming to reach the EFL Trophy quarter-finals for the first time since the 2020-21 season.
AFC Wimbledon EFL Trophy form:
W
W
L
W
AFC Wimbledon form (all competitions):
W
W
L
W
D
L
Oxford United EFL Trophy form:
W
L
W
W
Oxford United form (all competitions):
W
L
W
L
W
L
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Team News
Wimbledon duo Ali Al-Hamadi and Omar Bugiel are away on international duty, while Josh Neufville and Joe Lewis are unlikely to feature due to injury and illness respectively.
Defender Alex Pearce will have to be assessed after he was forced off in the first half of Saturday's FA Cup defeat with a thigh issue.
Despite being sent off against Ipswich, Harry Pell will be available for Tuesday's EFL Trophy tie, with his one-match suspension set to be served in Wimbledon's next league game.
As for the U's, their injury list features Sam Long, Stephan Negru, Greg Leigh, Josh Murphy, Marcus Browne and Kyle Edwards.
Buckingham could decide to rotate his squad, with the likes of James Henry, Stanley Mills, Alex Gorrin and Gatlin O'Donkor all in contention to start against Wimbledon.
Goodrham could also feature in the starting lineup after coming off the bench to score in Saturday's heavy FA Cup defeat to Coventry City.
AFC Wimbledon possible starting lineup:
Tzanev; Ogundere, Kalambayi, Johnson, Brown; Ball, Reeves, Pell; Tilley, Sasu, Davison
Oxford United possible starting lineup:
Eastwood; Smyth, Thorniley, Brown; Mills, Gorrin, McEachran, Bennett; Henry, Goodrham; O'Donkor
We say: AFC Wimbledon 1-2 Oxford United
Oxford may have won just one of their last five away games, but they have managed to beat Northampton Town and Forest Green on their travels in the EFL Trophy this season.
With that in mind, we think the U's will continue their away-day success in the competition by claiming a narrow win in Tuesday's contest.