Blades boss Kevin Blackwell is without several players; most notably club captain Chris Morgan (knee) who was stretcher off in the 1-1 draw with Hull City last weekend. His injury is not thought to be serious but it's expected that he won't make the visit to Home Park - Nick Montgomery will deputise as captain.
United will also be without midfielder Gary Speed (back) and defenders Ugo Ehiogu (Achilles) and Derek Geary (knee) who are all out for the remainder of the season.
The Blades will once again be without striker Darius Henderson who serves the last of a three match suspension after receiving a straight red card in the 2-1 away win at Southampton; he will be eligible to play in next Thursday's encounter at Hull City in the fifth round replay.
However the Blades can welcome back defender Leigh Bromby and strikers Jamie Ward and Arturo Lupoli who all missed the FA Cup tie with Hull City last weekend having being cup-tied.
Possible Blades Line-Up: Paddy Kenny, Kyle Naughton, Leigh Bromby, Matthew Kilgallon, Gary Naysmith, David Cotterill, Brian Howard, Nick Montgomery, Stephen Quinn, Greg Halford, Billy Sharp.
Pilgrims boss Paul Sturrock (ex-Sheffield Wednesday) will no doubt be under the cosh having not won a Championship fixture since Boxing Day 2008 when they recorded a 2-0 win at home to Southampton - since they they have claimed back to back draws away from home and dumped out of the cup by Arsenal.
The Home Park club will be without David McNamee (fractured cheekbone) and Belgian striker Emile Mpenza (hamstring), whilst David Gray (ankle) and Marcel Seip (groin) are hopeful of a return.
Possible Pilgrims Line-Up: Roman Larrieu, Kisztan Timar, Gary Sawyer, Mathias Doumbe, Craig Cathcart, Jim Paterson, Karl Duguid, Jamie Mackie, Alan Judge, Steven MacLean, Rory Fallon.