Manager Matt Bloomfield makes two changes to the side that drew 0-0 with Preston on Saturday.
Zack Nelson and Elijah Adebayo come into the starting XI, replacing Jacob Brown and Carlton Morris, who both drop to the bench.
The Hatters also welcome back Alfie Doughty to the squad in his first involvement since picking up an injury against Cardiff back in November.
Former Town man Peter Kioso starts for hosts Oxford.
Town: Kaminski, Hashioka, Bell, McGuinness, Holmes, Nakamba, Krauß, Clark, Jones, Nelson, Adebayo.
Subs: Krul, Walters, Andersen, Morris, Woodrow, Mpanzu, Brown, Walsh, Doughty.
Oxford: Cumming, Brown, Vaulks, Placheta, Brannagan, Harris, Phillips, Leigh, Dembele, Kioso, Helik.
Subs: Ingram, Long, Romeny, Sibley, Matos, Rodrigues, Ter Avest, Bradshaw, El Mizouni.
Referee: Stephen Martin