The 28-year-old has been ruled out after undergoing knee surgery and it could be a body blow to United's promotion aspirations.
The former Preston and Sheffield Wednesday striker, who missed three months of the season after rupturing his knee ligaments in September, was expected to feature at Leicester on Saturday, but Kevin Blackwell was forced to send him for surgery after he pulled up in training.
Cresswell's absence leaves Robbie Blake, David Healy and Rob Hulse as the main strikers,with Ian Moore also likely to come into contention.
Blackwell could now look to bring in a loan replacement ahead of the visit of Luton this weekend. He apparently has some irons in the fire.