The 26-year-old suffered a dislocated shoulder earlier this month but looked set for a January return to action before his shoulder popped out again, meaning he will have to go under the knife.
Manager Chris Wilder, who celebrated four years in charge of the U's on Friday, will also be without Adam Chapman, who fell awkwardly and injured his ankle in Tuesday's 2-0 FA Cup victory over Accrington.
Meanwhile, experienced defender Michael Duberry came through his late return to action against Accrington unscathed having not played since May.
But Simon Heslop is unavailable again as he serves the last game of his three-match ban.
Oxford are 18th in League Two ahead of their first-ever meeting with The Cod Army, eight points below the play-off places and eight above the relegation zone.
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- Adam Chapman
- dislocated shoulder