Last year's Shoguns Under-21's captain Richard Skuse is set to make his Premiership club debut at tighthead prop after Darren Crompton, Julian White and Emiliano Bergamaschi were ruled out.
But there is some good news for the club with Bristol's leading try-scorer, Brendon Daniel, set to make his first Premiership start for the Shoguns since January after recovering from a broken thumb. Felipe Contepomi, Craig Short and Matt Carrington are also included in the squad travelling to Northampton.
Commenting on the club's official website, Skuse, who has been on loan at Caerphilly said: "It has been a good learning curve playing in Wales. But playing for the Shoguns in the Zurich Premiership is what I've always wanted to do."
Skuse, who was born in Bristol and has represented all of the club's youth teams, added: "I'm hoping to put a foundation down for next season. Rhys Oakley made his debut last year and has gone on to become a regular this year."
The Shoguns are aware that Northampton will be keen to reverse their recent results. The team's Argentine scrum-half Agustín Pichot said: "The Saints will be keen to get back to winning ways after their last two results. Both their pride and emotions will have been hit and I'm sure they'll want to impress in front of their home crowd."
Bristol Shoguns (squad): Paul Johnstone, Andrew Sheridan, Chris Rowland, Saul Nelson, Richard Skuse, Garath Archer (captain), Scott Morgan, Alex Brown, Michael Lipman, Rhys Oakley, Craig Short, Matt Salter, Peter Richards, Agustin Pichot, Shane Drahm, Felipe Contepomi, Phil Christophers, Daryl Gibson, Andrew Higgins, Brendon Daniel, Matt Carrington, Jamie Williams, Lee Best.
Kick-off: 20.00 BST (19.00 GMT)