Speed, 39 hasn't featured in the first team since 25th November when the Blades lost 3-1 at Bramall Lane to Wolverhampton Wanderers when he was brought off early on with a back problem.
In the previous fixtures against Ipswich Town, Burnley, Nottingham Forest and Swansea City he has been rated at 50/50 but hasn't been fit enough to make the substitutes bench and it has been revealed he requires surgery.
Blades boss Kevin Blackwell said: "Gary's season is finished. It is a severe injury and a major blow which leaves us with a massive hole to fill in the side. It could be career threatening and Gary may now decide that's it.
"Wear and tear catches up with everyone in this game sooner or later and it's such a shame because he was enjoying his football and playing well. But Gary is in a lucky position and has options on his table.