Courtney Lawes and Dan Biggar return after skippering England and Wales respectively, while George Furbank is also back after starting at full-back against France last Saturday.
And Tommy Freeman, who made his comeback from a hamstring injury in the Premiership Rugby Cup win at Saracens last weekend, is able to take his place on the bench.
Saints are without two talented young props though, with Manny Iyogun and Ehren Painter ruled out.
That means Paul Hill, who will be making his 150th Saints appearance, starts at tighthead, while Alex Waller is at loosehead.
Matt Proctor remains sidelined, while Piers Francis has again been added to the unavailable list, so Saints go with Fraser Dingwall and Rory Hutchinson at centre this weekend.
As for London Irish, Will Goodrick-Clarke makes his 50th appearance for the club and is joined in the front row by Agustin Creevy and Ollie Hoskins.
Chunya Munga and Rob Simmons are named in the second row.
Matt Rogerson captains the team from the six jersey and is joined in the back row by Juan Martin Gonzalez and Seán O’Brien.
Nick Phipps and Paddy Jackson are the half-back duo, with Benhard van Rensburg and Lucio Cinti in the centres.
Ollie Hassell-Collins, Kyle Rowe and James Stokes start in the back three.
London Irish: Stokes; Rowe, Cinti, van Rensburg, Hassell-Collins; Jackson, Phipps; Goodrick-Clarke, Creevy, Hoskins; Munga, Simmons; Rogerson (c), Gonzalez, O’Brien.
Replacements: Cornish, Gigena, Green, Nott, Pearson, Cracknell, White, Parton.
Saints: Furbank; Skosan, Dingwall, Hutchinson, Collins; Biggar, Mitchell; Waller, Matavesi, Hill; Ribbans, Ratuniyarawa; Lawes, Ludlam (c), Augustus.
Replacements: Haywood, Auterac, Carey, Moon, Coles, James, Litchfield, Freeman.