Oxford have been boosted in their quest for an League Two play-off place by the return to full fitness of Damien Batt and Jon-Paul Pittman.
Both players missed the 1-1 draw at Plymouth last time out with minor injuries but return to contention at the Kassam Stadium, where Oxford need a win to stay in the race for a top-seven finish.
Doubts remain over striker James Constable, whose thigh strain will be assessed by the club before kick-off, and goalkeeper Ryan Clarke (rib). Wayne Brown is standing by to deputise for Clarke once again should he not make it.
Peter Leven is fit and available after a knee problem, but Tom Craddock (knee) and Alfie Potter (broken ankle) will not feature for the U's for the remainder of the campaign.
Meanwhile, Southend welcome Elliot Benyon back from suspension for this fixture.
The striker has completed a three-match ban for his dismissal at Bradford on Good Friday and will challenge for a place in Paul Sturrock's matchday 16.
Sturrock could keep faith with the same XI who clinched a superb 3-0 victory at home to Barnet last Friday night, although, despite still having an outside chance of automatic promotion, he may well be tempted to rotate one or two with the Shrimpers' play-off place already secure.
Long-term absentee Ryan Leonard is looking at making a comeback against Macclesfield on the final day of the season, while Christian Dailly (broken toe) and Blair Sturrock have also returned to training are set to be ready for possible play-off action.
Liam Dickinson (ankle), JP Kalala and Barry Corr (both knee) will not play again this term.