Making their season's debuts are Rob Appleyard and Craig Quinnell in the pack and, at fly-half, 18-year-old former captain of Wales' Schools, Gareth McCarthy.
Appleyard will be playing his first full game since injuring his neck last December.
Pieter Muller, Lee Abdul and Robin Sowden-Taylor, all of whom took the field as replacements against the Tigers, are also in the starting line-up while Jim Brownrigg moves from flanker to second row.
A mounting injury toll and international calls have led to prop Darren Sweet and scrum-half Owen Rutley being included among this week's replacements. Also called up are Cardiff under-21 products Leon Andrews, Richard Jones and James Malpas.
The Saints have announced a side that includes six full internationals. Former Queensland Reds' fly-half Shane Drahm partners All Black Mark Robinson at half-back and another new recruit, Renaud Peillard from Perpignan, plays at loose-head prop.
Cardiff Blues: Donavan van Vuuren; Lee Abdul, Nick Walne, Pieter Muller, Jonny Vaughton; Gareth McCarthy, Richard Smith; John Yapp, Andrew Lewis (captain), Kenneth Fourie, Craig Quinnell, Jim Brownrigg, Rob Appleyard, Nathan Thomas, Robin Sowden-Taylor
Replacements: Darren Sweet, T Rhys Thomas, Chris Stamatakis, Dan McShane, James Malpas, Owen Rutley, Leon Andrews, Richard Jones, Matt Allen
Northampton Saints: Nick Beal; James Brooks, Chris Hyndman, Mark Tucker, Bruce Reihana; Shane Drahm, Mark Robinson; Renaud Peillard, Dan Richmond, Chris Budgen, Rob Hunter, Mark Connors, Darren Fox, Andrew Blowers, Budge Pountney
Replacements: John Clark, Oriol Ripol, John Leslie, Johnny Howard, Ben Golding, Brett Sturgess, Matt Miles, Matt Lord, Jon Phillips, Grant Seely, Mark Soden, Wil Snape
Referee: Paul Adams (Ebbw Vale)