New signings Kahn Fotuali’i and Rob Verbakel will make their first appearances for Saints in the game at Bedford Blues on Friday night (kick-off 7.45pm).
Fotuali’i, a summer recruit from Ospreys, and Verbakel, who has joined from New Zealand outfit Otago, start at scrum-half and lock respectively.
Lions stars George North and Alex Corbisiero are not in the side as they continue to build match fitness ahead of the new season.
But Saints’ squad for the game at Goldington Road remains strong, with a number of England internationals involved.
Ben Foden starts at full-back, Luther Burrell is at centre and Courtney Lawes will take his place on the bench.
Also among the replacements is young prop Gareth Denman, who moved to Northampton from Rotherham during the summer.
Saints are expecting a good test and boss Jim Mallinder is looking forward to seeing his side in action for the first time since their Premiership final defeat to Leicester in May.
“The first competitive fixture is always a good chance to see where the squad is at in terms of preparation for the season,” said Mallinder.
“Obviously we still have over three weeks until the Premiership opener with Exeter and getting back out onto the pitch is the next step in being ready for the start of the new season.
“It is important that as many of the squad as possible see game time over the coming weeks’ fixtures and as a side who regularly compete at the top of the Championship, Bedford are a quality outfit who will provide a tough challenge.”
Saints: Foden; Elliott, G Pisi, Burrell, K Pisi; Wilson, Fotuali’i, E Waller, McMillan, Mercey; Craig, Verbakel; Dowson (c), Nutley, van Velze.
Replacements: Artemyev, Diggin, Collins, Stephenson, A Day, Mallinder, Glynn, A Waller, Haywood, Denman, Lawes, C Day, Clark, Harrison, Dickinson.