While the hosts are currently leading the way in League One, the U's are sitting just outside the playoffs in seventh place.
Match preview
Portsmouth saw their four-game winning run come to an end with a goalless draw in last Saturday's away meeting with Charlton Athletic.
Despite missing out on maximum points, Pompey extended their lead at the top to seven points after promotion rivals Derby County and Bolton Wanderers fell to defeats last weekend.
Matters got even better for Portsmouth in midweek as Derby and Bolton both lost games in hand to leave Portsmouth in a promising position with 11 games left to play in the season.
While they will be tested by a playoff contender this weekend, John Mousinho's side will take confidence from the fact they won their last three home matches, scoring at least three goals in each of those victories.
Portsmouth have managed to avoid defeat in four consecutive matches against Oxford, although their last three meetings have finished all square.
In contrast to their hosts, Oxford have found wins hard to come by in recent weeks, having won just one of their last nine matches.
Des Buckingham's charges experienced a disappointing outing last weekend as they gave up a slender lead to lose 2-1 to fellow playoff hopefuls Leyton Orient.
Tyler Goodrham saw his 20th-minute opener cancelled out by Ollie O'Neill in the opening stages of the second period, before George Moncur scored the winning goal to end Oxford's six-game unbeaten run (W1, D5).
Oxford dropped out of the top six in midweek following Stevenage's 1-0 win over Cambridge, leaving the U's two points adrift of Steve Evans's side.
With Oxford desperate to get their playoff bid back on track, they will be hoping to claim their first away win over Portsmouth since recording a 1-0 win in January 2016.
Portsmouth League One form:
D
W
W
W
W
D
Oxford United League One form:
D
D
W
D
D
L
Team News
Portsmouth are having to cope with a lengthy injury list which features Joe Morrell, Alex Robertson, Tom Lowery and Ben Stevenson.
The hosts are also unable to call upon the services of Zach Swanson, Tom McIntyre, Regan Poole, Terry Devlin and Tino Anjorin.
Despite seeing his side play out a goalless draw last weekend, Mousinho could stick with an unchanged lineup for Saturday's home fixture.
As for the visitors, defender Elliott Moore could be brought into the starting lineup after recovering from a hip problem.
Marcus McGuane returned from injury to feature as a substitute last weekend, and the midfielder is in contention to start against the league leaders.
Mark Harris is expected to retain his place up front, and the former Cardiff City striker will be looking to add to the nine league goals he has scored this season.
Portsmouth possible starting lineup:
Norris; Rafferty, Raggett, Shaughnessy, Ogilvie; Moxon, Pack; Kamara, Lang, Lane; Bishop
Oxford United possible starting lineup:
Cumming; Long, Moore, Brown, Leigh; Brannagan, McGuane; Murphy, Rodrigues, Goodrham; Harris