Sam Dickinson is set to make his first Saints appearance since returning to the club this summer.
The 32-year-old lines up at No.8 against London Irish at the Madejski Stadium on Sunday (kick-off 3pm), with Mitch Eadie (ankle) and Teimana Harrison (shoulder) both injured.
Dickinson was released by Saints at the end of last season, but with Louis Picamoles having switched to Montpellier, the former Rotherham man was handed a new short-term deal.
He will remain at Franklin's Gardens until the start of the new year, when South Africa flanker Heinrich Brüssow will arrive following the conclusion of his club commitments in Japan.
Dickinson, who played a key role in Saints' 2013/14 double-winning season, captained the Wanderers to Aviva A League glory last season.
And he will now aim to make his mark, by taking his second chance against Irish as Jim Mallinder's men look to make it three wins in a row.
Dylan Hartley, Tom Wood, Piers Francis and Stephen Myler will again be missing from the matchday 23 at the Madejski Stadium.
Hartley (hand) and Francis (jaw) are close to full fitness, while Wood (shoulder) and Myler (knee) are even nearer to returning and they will be travelling reserves for the game in Reading.
Courtney Lawes again captains the side after leading them to a comprehensive 24-6 Aviva Premiership victory against Bath at the Gardens last Friday.
For London Irish, Johnny Williams returns to play at inside centre having recovered from a hamstring injury sustained towards the end of last season.
That is one of five changes to the side that was beaten at Sale Sharks last weekend.
Fijian international wing Napolioni Nalaga is set for his full debut, with the former Lyon and Clermont Auvergne favourite taking the No.11 shirt.
A new-look forward pack will be spearheaded by skipper Ben Franks, with Petrus Du Plessis replacing injured former Saint Danny Hobbs-Awoyemi in the front row.
Josh McNally comes in for Mike Coman at blindside flanker, while Conor Gilsenan gets the nod at openside flanker and Blair Cowan switches to No. 8.
London Irish: Bell; Lewington, Tikoirotuma, Williams, Nalaga; Marshall, McKibbin; Franks (c), Porecki, Du Plessis; van der Merwe, De Chaves; McNally, Gilsenan, Cowan.
Replacements: Paice, Elrington, Hoskins, Paulo, Schatz, Steele, Tonks, Ojo.
Saints: Tuala; North, Horne, Burrell, Collins; Mallinder, Groom; Waller, Haywood, Hill; Paterson, Ribbans; Lawes (c), Gibson, Dickinson.
Replacements: Marshall, Ma'afu, Brookes, Day, Ludlam, Reinach, Grayson, Foden.