Louie Sibley will be out for at least the next four weeks after picking up an ankle injury.
The midfielder made his first Championship start of the season in Saturday’s 2-1 home defeat by Swansea but then missed Tuesday’s win over Hull City.
“My injury board has got too many names on it at the moment,” Oxford manager Des Buckingham told BBC Radio Oxford.
“Louie (Sibley) went over on his ankle in training on Monday and will be out for four to six weeks.
“Ben Nelson had to come off tonight (against Hull) and we’ll assess him and decide whether we need to send him for a scan.”
Oxford’s victory against Hull City was their first in nine Championship games and they are now preparing for a trip to Watford on Friday.
“We are really testing the depth of our squad, Jordan Thornley has been out with an ankle injury which he sustained two or three months ago and has been coming back from that.
“We are eight or nine starting players light which impacts us more than it might other teams in this league but we won’t use that as an excuse,” added Buckingham.