Willett caused a huge shock at Augusta last year by clinching the Masters - his maiden major - after taking advantage of a sensational back-nine collapse from defending champion Jordan Spieth.
However, the Englishman has struggled ever since he won the famous Green Jacket and has yet to pick up another title on either the European Tour or PGA Tour.
The Sheffield-born star has only recorded one top-10 finish in 2017, at the Maybank Championship, and his form is scratchy as the Masters in Georgia edges closer.
Willett was hoping to warm up at the Arnold Palmer Invitational, which started on Thursday, but has been taken ill.
"Really sad to withdraw," the Englishman said on Twitter. "I've been up all night with terrible sickness. Not ideal but felt it worse... to take spot from reserve if I wasn't able to finish."