Welsh internationals Martyn Williams, Gethin Jenkins, Tom Shanklin and Andy Powell have all been given a well earned rest while Kiwi fullback Ben Blair and inspirational second row Paul Tito have also been given time off.
Leigh Halfpenny makes his second start for the Blues at full back with young scrum half Darren Allinson also starting for the third time.
In the forwards, there is new partnership in the second row with Scott Morgan and Bradley Davies starting. The back row also has a new feel with Maama Molitika starting at No 8, Ben White at 6 and Robin Sowden Taylor, captaining the side at openside flanker.
Although he will be watching from the sidelines for the first of the Welsh derbies, Jenkins is confident the Blues have the firepower to make their mark.
"We definitely want to be the top Welsh region, whether it be in the Magners League competition or the Heineken Cup," he said.
"We have not had a good start in the Magners League, but we will be looking to address our position in the next three Welsh derbies.
"They are tough affairs and they are always pretty scrappy, but we are going out there to get a few wins. We have a good squad and they can go out and do a job over Christmas, starting with the match at the Scarlets tomorrow evening."
15 Leigh Halfpenny 14 Richard Mustoe 13 Jamie Robinson 12 Gareth Thomas 11 Tom James 10 Ceri Sweeney 9 Darren Allinson; 8 Maama Molitika 7 Robin Sowden Taylor (capt) 6 Ben White 5 Scott Morgan 4 Bradley Davies 3 Taufa'au Filise 2 T Rhys Thomas 1 John Yapp
Replacements: 16 Gary Powell 17 Gareth Williams 18 Deiniol Jones 19 Damian Welch 20 Jason Spice 21 Nicky Robinson 22 Chris Czekaj