The Blues left-back, who has been troubled with knee injuries for the last 18 months, will undergo surgery on a rupture of his patella tendon and will be out for at least six months, reports in the Birmingham Evening Mail say.
Grainger returned to the first team squad for the game against Middlesbrough back on March 20th - his first taste of Premiership football since January 2003.
He had been on-loan at first division Coventry City but was recalled by manager Steve Bruce because of injuries to other players.
Four games into his return to first team action he lasted for just over thirty minutes of the first half against United having replaced Stan Lazaridis after twelve minutes, a game in which he scored from a trademark free-kick.
This latest setback is sure to raise question marks as to whether the poular 31-year-old full-back will ever don the Royal Blue shirt again although it won't be for the want of trying I'm sure.