Heinrich Brüssow will be back in action for Saints when they travel to Wasps in the Premiership Rugby Cup on Sunday (kick-off 3pm).
The South African flanker has not played since the defeat to Saracens on September 15 due to concussion.
But he is available again this weekend and will line up in the seven shirt at the Ricoh Arena.
Jamie Gibson, who will be the skipper, Api Ratuniyarawa, Ben Franks and James Fish are also back in the pack, while Charlie Davies makes his first Saints start at scrum-half.
Fraser Strachan also gets a first start in the first team, with Luther Burrell given a rest this weekend.
The other change comes on the wing with Andrew Kellaway replacing Matt Worley, who sustained concussion in the 51-24 win against Bristol Bears last Saturday.
Amongst the replacements there is room for Toby Trinder, Alex Coles, Paddy Ryan, Connor Tupai and Josh Gillespie, all of whom would make their senior Northampton debuts if they enter the fray – with Gillespie hoping to become the youngest Saint in the professional era at 18 years and 15 days old.
For Wasps, tighthead prop Jake Cooper-Woolley will return to make his first appearance since the Premiership semi-final in May, while Kiwi wing Ambrose Curtis prepares for his first-team debut.
Rob Miller returns at full-back to skipper the side for the first time and is joined by Curtis and the returning Marcus Watson in the back three.
Gaby Lovobalavu recovers from a knee problem to start in the centres with Ross Neal, while Billy Searle and Craig Hampson form the half-back combination.
In the pack, Tom West gets his first start of the season alongside Cooper-Woolley and Academy hooker Gabriel Oghre, while Charlie Matthews and Kearnan Myall are handed their first starts of the campaign in the second row.
In the back row, Ben Morris also gets his first start of the season alongside Joe Atkinson and Tom Willis.
On the bench, loosehead Simon McIntyre could make his first appearance since suffering a foot injury in April while Antonio Harris could also step in for his first game since the Premiership semi-final in May following a bicep problem.
Wasps: Miller (c); Watson, Neal, Lovobalavu, Curtis; Searle, Hampson; West, Oghre, Cooper-Woolley; Matthews, Myall; Morris, Atkinson, Willis.
Replacements: Harris, McIntyre, Hunt, Cardall, Seabrook, Porter, Simonds, James.
Saints: Furbank; Kellaway, Dingwall, Strachan, Sleightholme; Grayson, Davies; van Wyk, Fish, Franks; Ratuniyarawa, Barrow; Gibson (c), Brüssow, Eadie.
Replacements: Marshall, Trinder, Garside, Coles, Onojaife, Ryan, Tupai, Gillespie.