Lewis Ludlam will make his first Champions Cup start for Saints in Saturday's clash with Ospreys at Franklin's Gardens (kick-off 5.30pm).
The flanker, who recently made a successful return from glandular fever for the Wanderers, will make his first appearance for the first team since the win against Bath on September 15.
Ludlam is one of eight fresh faces in the Saints side, with boss Jim Mallinder making a host of changes to the side that lost 24-22 to Newcastle Falcons at the Gardens last Friday.
Luther Burrell makes his comeback after suffering concussion at Worcester last month, while David Ribbans and Christian Day also return from injury to start in the second row.
Francois van Wyk comes in for the injured Alex Waller (broken arm), while there is a new half-back pairing, with Nic Groom and scrum-half and Piers Francis at 10.
Ahsee Tuala will look to celebrate the contract extension he signed earlier this week by starring on the wing.
Meanwhile, Ospreys have not been able to name Dan Biggar in their matchday squad as he is undergoing a HIA (head injury assessment).
Biggar will join Saints in the summer of 2018 but will play no part against his future employers this weekend.
Ospreys have a number of injury issues, with Wales pair Justin Tipuric and Rhys Webb among those also ruled out.
Saints: Mallinder; Tuala, Horne, Burrell, Foden; Francis, Groom; Van Wyk, Hartley (c), Ford-Robinson; Ribbans, Day; Lawes, Ludlam, Harrison.
Replacements: Haywood, Ma'afu, Hill, Paterson, Gibson, Reinach, Myler, Estelles.
Ospreys: Evans; Dirksen, Fonotia, Watkin, Hassler; S Davies, Habberfield; Smith, Baldwin, Arhip; B Davies, Wyn Jones (c); Lydiate, Cracknell, King.
Replacements: Otten, Jenkins, Fia, Beard, McCusker, Morgan-Williams, Hook, John.