The 35-year-old striker, who had not been involved in the Blades last three matches, has undergone surgery on a thigh injury sustained in training.
Sharp said in an Instagram post on Wednesday: "Always gutting to miss games so to be ruled out for the remainder of the season hurts.
"Sadly the injury was worse than I'd hoped but operation went well and will be back stronger next season to get my 250th goal in front of a packed Bramall Lane."
Sharp scored the 249th goal of his professional career in a 1-0 FA Cup win over Bristol City in February.
He has netted 98 times for the Blades since rejoining them in 2015 for a third spell with the club.
Two more of United's promotion heroes of 2018-19 are out of action in Chris Basham and Jack O'Connell, while record signing Sander Berge has been sidelined since December with a hamstring issue.