The visitors, who currently occupy seventh position, will be looking to return to winning ways after losing their last two matches.
Match preview
Oxford will be determined to finish January on a high note after experiencing a number of disappointing results this month.
They may have kicked off the year with a win over Charlton Athletic, but the U's went on to exit both the FA Cup and the EFL Trophy.
Although they claimed a 3-1 victory over Carlisle United, Des Buckingham's side have fallen to defeats in their last two outings, losing 1-0 to Barnsley and 3-1 in Saturday's away clash with Bristol Rovers.
As a result of their unsuccessful trip to the Memorial Stadium, the U's have been replaced in the final playoff position by Stevenage due to goal difference.
Having lost their last two home matches against Derby County and Barnsley, Oxford will be looking to claim their first home win since Boxing Day when they play host to the league leaders.
In contrast to their opponents, Portsmouth will head into Tuesday's contest in a positive mood after claiming consecutive 1-0 victories in away meetings with Fleetwood Town and Port Vale.
After edging out the Cod Army, Pompey looked set to play out a goalless draw with the Valiants until Colby Bishop dispatched an 88th-minute penalty to snatch all points.
As a result of Bishop's 14th goal of the season, John Mousinho's side remained top of the League One table with a two-point buffer to second-placed Bolton Wanderers, while they are three points better than Peterborough United and Derby County, who occupy their and fourth spot respectively.
Pompey may relish the chance to embark on a third consecutive away trip, having collected 31 points from their 15 road trips to leave them with the best away record in the division.
The visitors will be looking to produce another strong defensive display after keeping nine clean sheets in 15 away league games this season.
Oxford United League One form:
W
L
W
W
L
L
Oxford United form (all competitions):
W
L
L
W
L
L
Portsmouth League One form:
D
W
L
L
W
W
Team News
Oxford are expected to be without the services of Sam Long and Joe Bennett, who missed Saturday's clash with Bristol Rovers due to head and calf injuries.
After dropping down to the bench at the weekend, Marcus McGuane may be brought back into the Oxford midfield for Tuesday's home contest.
Millwall loanee Tyler Burey could be presented with his first start for the U's after featuring as a substitute in his first two matches with the club.
As for the visitors, they are unable to call upon Regan Poole, Alex Robertson, Zach Swanson, and Tino Anjorin, while Kusini Yengi is still on international duty with Australia after his country progressed to the quarter-final of the Asian Cup.
Midfielder Marlon Pack missed Saturday's win through illness, but Mousinho will hope to have his captain back for the midweek away trip.
January addition Myles Peart-Harris made his Pompey debut at Vale Park, and the Brentford loanee is expected to retain his place in the side.
Oxford United possible starting lineup:
Cumming; Stevens, Moore, Brown, Leigh; McGuane, Brannagan; Goodrham, Rodrigues, Burey; Harris
Portsmouth possible starting lineup:
Norris; Devlin, Shaughnessy, Raggett, Ogilvie; Morrell, Pack; Kamara, Peart-Harris, Lane; Bishop