Butler's absence will be most keenly felt, with Richard Hinds set to drop back from his regular midfield berth to partner Andy Crosby.
This opens up a gap in midfield - Ryan impressed against Tranmere in midweek and could keep his place, while Matty Sparrow could also be moved into the middle with Cleveland Taylor coming into the starting XI.
Southend arrive at Glanford Park minus star striker Freddy Eastwood, who starts a four game ban for violent conduct.
The Shrimpers were promoted along with United last season, winning the play-offs, and defender Adam Barrett admits he has noticed the step-up in class compared to last season.
He said: "I've noticed that the tempo is quick and once you gave the ball away it was much harder to get it back than we had been used to.
"But we have adjusted now and I think that has shown."