James Craig will make his first appearance of the season when Saints host Gloucester in an Anglo-Welsh Cup clash at Franklin's Gardens on Saturday (3pm).
Craig had been on the England Saxons tour of South Africa during the summer, but concussion has seen him sidelined at the start of the current campaign.
But the lock will start against Gloucester, with Api Ratuniyarawa on international duty with Fiji.
Jordan Onojaife, who started at six in the 24-16 win at Newcastle last Sunday, is also in the second row, with Christian Day not in the squad.
Sam Dickinson will make just his second start of the season, skippering Saints from No.8.
Jamie Elliott, who came off the bench last weekend, gets his first start of the season, replacing Howard Packman on the wing.
Teimana Harrison is among a strong set of replacements following his release by England earlier in the week.
Lee Dickson and Ben Foden are also on the bench, along with Ben Nutley, who is set to make his first appearance of the campaign after recovering from injury.
Meanwhile, Salesi Ma'afu will make his first appearance at the Gardens since leaving Saints for Toulon during the summer of 2015.
The Australian tighthead prop, who was a Premiership and Challenge Cup winner at Saints, will start for Gloucester.
The Cherry and Whites make five changes from their 36-32 win against Saracens, with hooker Henry Walker making his full debut and No.8 Gareth Evans making his first appearance of the season.
Saints: Wilson; Elliott, Burrell, Hutchinson, Collins; Olver, Kessell; E Waller, Clare, Hill; J Onojaife, Craig; Gibson, Ludlum, Dickinson (c).
Replacements: Fish, Beesley, Denman, Paterson, Harrison, Nutley, Dickson, Foden.
Gloucester: L Evans; Protheroe, Purdy, Creed, Thorley; Burns, Braley; Y Thomas, Walker, Ma'afu; Batley, Latta; Ludlow (c), G Thomas, G Evans.
Replacements: Mullis, Hohneck, Knight, Beckett, Clarke, Vellacott, Hudson, Safe.