Borthwick captained the World Cup finalists to a narrow RBS 6 Nations victory over Italy in Rome last weekend, replacing stomach bug victim Phil Vickery as skipper.
But it is now Borthwick's turn to give England head coach Brian Ashton cause for concern.
An injury-ravaged RBS 6 Nations campaign has already seen Ashton lose the likes of Mike Tindall, David Strettle, Lewis Moody and Tom Rees.
And Borthwick's knee problem will now come under close scrutiny ahead of England tackling tournament favourites France in Paris next Saturday.
Borthwick, who suffered the injury against Italy, failed to come through a club fitness test on Friday.
He will be replaced in the second-row against Wasps by Peter Short, with centre Alex Crockett captaining the side.
Borthwick's England colleagues Lee Mears, Matt Stevens and Michael Lipman, meanwhile, all feature in the Bath starting line-up.