On top of injuries to Michael Raynes and Jake Wright, the U’s are also without Tom Newey, who is beginning a two-game suspension.
David Lynn is the only like-for-like replacement, but the 19-year-old has only made one senior appearance.
The alternative is playing somebody out of position or changing to a back three.
Caretaker boss Lewis admitted it gave him a problem, saying: “It does a little bit and we might have to shuffle it around.”
The only new injury doubt is Dave Kitson, who tweaked a hamstring in Tuesday’s 3-2 loss at Newport County.
Morecambe have to make a change from Tuesday’s 1-1 draw at Exeter City, where Jamie Devitt was sent off.
Alex Kenyon is likely to replace the midfielder, while Shaun Beeley could return.
Morecambe: from Roche, Beeley, Parrish, Hughes, Threlfall, Kenyon, Fleming, Williams, Amond, Sampson, Ellison, Redshaw, Arestidou, Coyle, Diagne, Drummond, McGee.
Oxford Utd: from Clarke, Bevans, Hunt, Mullins, Lynn, Wroe, Rose, Ruffels, Smalley, Constable, Connolly, Kitson, Marsh, Potter, Williams, O’Dowda, Davies, Long, Ashby, Henly.