The visitors, meanwhile, are looking to get back to winning ways, after losing in dramatic fashion last time out in the FA Cup clash against Exeter City.
Match preview
Oxford United were denied the three points in midweek against Shrewsbury Town courtesy of Matthew Pennington's third goal of the season, meaning the U's failed to make it two consecutive away wins on the spin.
Cameron Brannagan had put the visitors ahead in the first half with his sixth league goal of the campaign but Pennington's header was enough to haul Steve Cotterill's men into the top 10 in League One.
Oxford have so far been unable to replicate their form in the 2021-22 season, in which they recorded a very respectable eighth-placed finish, and they currently find themselves languishing in 16th in the table with just over a third of the season gone.
Performances at the Kassam Stadium in particular have been an issue this season, as Oxford are 20th in the league for points acquired at home, picking up just eight in eight league outings.
However, the U's are currently on a four-game unbeaten run, so Karl Robinson will be eager to see his side pick up their first three points at home here since their victory over Burton Albion on September 3.
Meanwhile, Archie Collins stunned Port Vale with a superb 89th-minute goal to secure a 3-2 FA Cup first-round victory for Exeter City over their League One rivals at Vale Park last time out.
Port Vale thought they had secured a replay when Dan Butterworth found the back of the net from substitute Mal Benning's low cross with three minutes remaining.
However, Collins bent home from 25 yards to earn Gary Caldwell a first win as Exeter boss in the Scot's third game in charge - and book a second-round spot for the Grecians for a fourth consecutive season.
Domestically, the Valiants are in mixed form, taking 11 points from the 18 available in their last six outings, however, Darrell Clarke will be pleased with his side's performances up until this point, as they sit 11th in League One, four points off the playoff places.
These two sides last met in the FA Cup back in the 2017-18 season, where Port Vale prevailed as 2-0 winners, and they will be eager to repeat that outcome here.
Oxford United League One form:
W
L
D
W
D
D
Oxford United form (all competitions):
L
L
D
W
D
D
Port Vale League One form:
W
D
W
L
W
D
Port Vale form (all competitions):
W
W
L
W
D
L
Team News
Oxford's extensive injury list has been added to after Kyle Joseph was stretchered off during the club's draw at Shrewsbury.
Djavan Anderson also appeared to break his hand inside the opening two minutes at Montgomery Waters Meadow, but the former Lazio man was able to see out the remainder of the game. However, Robinson fears the injury is worse than initially thought, meaning Anderson could be absent here.
Saturday's tie with Port Vale appears to have come too soon for Sam Long as he continues to recover from a hamstring injury, while Cameron Brannagan looks set to keep his place in midfield after his performance away in Shropshire last time out.
Meanwhile, Darrell Clarke made several changes for the FA Cup tie against Exeter, so he may look to rotate his side again here.
James Wilson was on the scoresheet for Vale against Wycombe Wanderers, so he could return up top, or Clarke may stick with Dennis Politic, who scored his fourth goal of the season against Exeter.
Oxford United possible starting lineup:
Eastwood; Seddon, Moore, Findlay, Brown; Bate, Brannagan, McGuane; Anderson, Smith, Browne
Port Vale possible starting lineup:
Stevens; Jones, Hall, Cass; Robinson, Conlon, Massey, Pett, Benning; Harrison, Wilson
We say: Oxford United 0-1 Port Vale
Port Vale have won or drawn four of the last five matches they have played away from home, while Oxford have lost four of the last five fixtures they have hosted at the Kassam Stadium.