Rovers have a game in hand and are eight points clear of Rochdale, who sit on the edge of the relegation spots with 46 points.
The home team have not lost a game since the end of February, a 2-1 defeat at Yorkshire rivals Rotherham United.
It was only their third reversal in the past 19 league games, form that has seen Doncaster move towards securing another season in League One following their promotion last year.
Oxford will be hoping to inflict the hosts’ first defeat in seven games as they also chase points to remain in the division.
The U’s have accrued a mere nine points in their last 13 league games with two wins and three draws.
This has left both the club and their fans apprehensive as they only have a four-point buffer between Oxford and the relegation spots.
For Rovers, Tuesday’s 3-3 draw against relegated Bury, who had lost their previous seven games, was seen as a missed opportunity.
Looking to today’s game, Doncaster’s assistant manager Gavin Strachan said: “We have come up against Karl Robinson’s sides a few times this season.
“There is usually a clear identity to how they have played, and they have played a little differently of late. They are a team that are full of energy, and they have two very strong strikers, if he chooses to use them. They have good experience and strength at the back.
“It has all the ingredients to be an exciting game, and hopefully it is, but I hope that we can make better decisions on the day.”
Oxford lost 1-0 to high-flying Wigan Athletic on Tuesday, with United manager Robinson commenting: “It’s important that we are right mentally as well – mental fatigue is the one (worry), maybe, but it’s our job as a staff to make sure that isn’t a factor.
“It’s a massive game for us and we have to make sure we are ready to go and that our energy levels are really high. Three or four players didn’t travel to Wigan on Tuesday so they will be fresh, but I’ve seen no signs of tiredness in the group at all. So they will get themselves ready and it’s one everyone is looking forward to.”