Oxford are impressing in their first season at this level since the turn of the millennium, while Luton have been uninspiring since dropping down from the Premier League.
Match preview
When Luton were promoted to the top flight, the plan appeared to be to use the money to invest in the club, and build a squad that will be able to return immediately if they were relegated.
Unfortunately for the Hatters, they did suffer relegation, but the squad they have assembled is struggling on their return to the second tier.
After taking just one point from their opening four games, it appeared Luton had turned a corner, with back-to-back wins against Millwall and Sheffield Wednesday, but they were woeful on Friday night, handing Wayne Rooney's Plymouth Argyle their second win of the season.
That 3-1 defeat means Luton ended the weekend down in 19th, and the omens do not appear promising ahead of their next encounter.
Luton have failed to win any of their previous six matches against newly-promoted sides, losing here to Sheffield United and Burnley in the top flight last season.
That tough season in the Premier League also meant they went the whole campaign without winning consecutive home games - a record they can put straight with a win here, after their success against Sheffield Wednesday two weeks ago.
Oxford are a club the Hatters have enjoyed great success against when they have gone head-to-head, but it will be the first meeting since the final day of the 2018-19 season, when Luton's 3-1 win sealed the League One title.
Luton are unbeaten in 15 meetings, having not suffered defeat against their upcoming opponents since November 1992, and you have to go back a further five-and-a-half years for Oxford's last win at Kenilworth Road.
That is not promising for an Oxford side that have lost all of their away games so far this season, meaning this could be just the fifth time in their history that they fall to defeat in their opening four on the road.
Poor away form does not mean they have had a bad start by any means though, as only Blackburn Rovers have a better home record than Des Buckingham's side so far - taking 10 points from a possible 12.
For a club that were not fancied to get out of League One last season, they are overachieving in their first season as a second-tier club since 1999.
The visitors enter the midweek round of fixtures still in the top half, even if their 100% home start was ended by drawing 0-0 against Burnley at the Kassam Stadium on Saturday.
When put in context, it is an exceptional start by the U's, who were a non-league club at the start of 2010s, but whether their current style of play is sustainable is up for question, considering Burnley outshot them 16-3 at the weekend, and were unable to score.
Luton Town Championship form:
D
L
L
W
W
L
Luton Town form (all competitions):
L
L
L
W
W
L
Oxford United Championship form:
L
L
W
W
L
D
Oxford United form (all competitions):
L
L
W
W
L
D
Team News
Luton were handed a double blow in their defeat to Plymouth on Friday, as both Teden Mengi and Mads Andersen were forced off early, meaning defensive numbers could be dwindling, with Daiki Hashioka also out.
Shandon Baptiste remains out with a hamstring problem, but manager Rob Edwards was able to call upon Jacob Brown for the first time in over seven months, coming on as a half-time substitute at Home Park.
One positive that came out of Friday's defeat was the fact Victor Moses scored his first goal for the club, and the ex-Chelsea and Liverpool man could come into the starting XI here.
Oxford are set to remain without key player Cameron Brannagan, who has missed the last two games with a muscle problem, while Matt Phillips and Will Goodwin are also sidelined at present.
Josh McEachran was a doubt after being forced off early against Bristol City just over a week ago, and the midfielder was an unused sub versus Burnley, but could be able to return here.
Joe Bennett is the other injury concern for the visitors, and he will remain out until the new year after suffering a nasty ankle injury at the end of August.
Luton Town possible starting lineup:
Kaminski; Walters, McGuinness, Burke; Moses, Krauss, Clark, Doughty; Z Nelson, Adebayo, Chong
Oxford United possible starting lineup:
Cumming; Kioso, Moore, Brown, B Nelson; Vaulks, Rodrigues, El Mizouni; Goodrham, Harris, Dembele
We say: Luton Town 2-1 Oxford United
Both teams have scored in the last six meetings between these two sides, and while neither have been particularly ruthless in attack so far, that is likely to happen again.