The relegation-threatened hosts are languishing in 23rd place, while playoff-chasing Oxford are sitting in eighth position.
Match preview
Port Vale have drawn four and lost nine of their last 13 matches since claiming their most recent victory over Blackpool at the end of 2023.
Darren Moore has been unable to spark an upturn in fortunes in his seven games in charge, but he at least saw his side take a point from Tuesday's away meeting with Leyton Orient.
The Valiants played out a goalless draw at Brisbane Road to end a dismal run of five consecutive away defeats and pick up their first away point since December.
Although they managed to avoid a defeat in midweek, Port Vale are second from bottom and six points adrift of safety with 10 games left to play.
With the Valiants low on confidence, they may look to use the reverse fixture as a source of inspiration after they recorded a 2-1 when the two sides met at the Kassam Stadium in September.
Oxford, meanwhile, will have to pick themselves up from a demoralising 5-0 defeat in Tuesday's away meeting with promotion-chasing Bolton Wanderers.
The U's have now lost three of their last four matches, while they have only won twice in their previous 12 league games.
Despite finding wins hard to come by, Des Buckingham's side are still in the hunt for a playoff finish with just one point separating them from sixth-placed Stevenage, who have a game in hand over the U's.
Having taken just two points from their last five away matches, Oxford need to quickly improve on their travels if they are to achieve a top-six finish.
After failing to win any of their previous five away games against Port Vale, the U's will be hoping to leave Vale Park with a victory for the first time since March 2011.
Port Vale League One form:
L
L
D
L
L
D
Oxford United League One form:
D
D
L
L
W
L
Team News
The hosts are expected to be without the services of full-back Mitch Clark and forward Uche Ikpeazu due to their respective injury issues.
Following Tuesday's hard-earned goalless draw, Moore could opt for consistency and select an unchanged starting lineup.
Ryan Loft should be on the bench after returning from a two-game injury absence to be an unused substitute for the midweek clash with Leyton Orient.
As for the U's, Buckingham is expected to have the majority of his squad available, although Tyler Goodrham is likely to miss a fourth straight game through injury.
Full-back Sam Long is in contention to start Saturday's contest after being introduced as a half-time substitute in midweek.
Mark Harris is set to retain his place up front, and the former Cardiff City man will be looking to add to the nine league goals he has scored this season.
Port Vale possible starting lineup:
Ripley; Debrah, Smith, Jones; Sang, Ojo, Lowe, Mighten; Garrity; Massey, Wilson
Oxford United possible starting lineup:
Cumming; Long, Moore, Brown, Leigh; McGuane, Brannagan; Dale, Rodrigues, Murphy; Harris