Seacrest said that the British music mogul, 48, has undergone so many treatments he is finding it difficult to put on his infamous scowl while watching talent auditions, reports the Sun.
American TV presenter Seacrest, 33, mocked Cowell's love for the face-freezing injection on U.S. TV programme The Ellen DeGeneres Show.
When asked by Ellen DeGeneres if Cowell would be just as 'angry' as in previous series, Seacrest replied: 'You wouldn't know because of all the shots.'
'The angry face is the same as the happy face,' he added.
Cowell has been long open about his love for Botox and believes there's nothing wrong with trying to better your appearance.
He said: "To me, Botox is no more unusual than toothpaste. It simply works. You do it once a year - who cares?"
The multi-millionaire pop mogul also admitted to having had veneers put on his teeth.
"I am definitely vain. But to be honest with you, I can't think of one person on TV who isn't," he added.