Mkandawire, predominantly a midfielder but who has been playing at centre-back in recent matches, is now back with parent club Millwall after completing his loan spell with Tuesday's 2-0 victory at Aldershot - boss Phil Brown's first win since taking charge.
Prosser, meanwhile, has missed the last two matches due to a back injury but is back in the fold for the clash at Bootham Crescent. He will now compete with Mark Phillips and Chris Barker for a place alongside Ryan Cresswell.
Goalkeeper Paul Smith will be assessed having missed out at the EBB Stadium in midweek with a virus.
Despite just one victory in their last eight games, Southend still harbour an outside chance of a play-off place as they currently sit four points off the top seven with two matches remaining.