Dom Barrow will make his return from injury when Saints take on Timisoara Saracens at Franklin's Gardens on Friday night (kick-off 8pm).
The lock has been blighted by concussion and a hamstring tear since arriving at Saints last summer, allowing him to make just five appearances so far.
But Barrow is now fully fit again, meaning he is able to line up alongside David Ribbans in the second row for this week's final Challenge Cup pool game.
Nafi Tuitavake is also ready to return, having been named among the replacements.
The Tongan back has only made one appearance this season, starting in the opening-day defeat at Gloucester before a neck injury sidelined him.
Saints have made a total of 12 changes to the team that lost an eventful European encounter 48-40 at Clermont Auvergne last Saturday.
Luther Burrell, Ribbans and Alex Mitchell are the only players who remain from the starting 15 at Stade Marcel Michelin.
Alex Waller returns to captain the team, while Paul Hill is also part of the front row.
Jamal Ford-Robinson is on the bench and set to make his second appearance of the season after a knee injury.
Saints know that if they pick up the expected bonus-point success on Friday night, they will face an away quarter-final at the end of March.
Saints: Furbank; Sleightholme, Hutchinson, Burrell, Kellaway; Grayson, Mitchell; Waller (c), Marshall, Hill; Ribbans, Barrow; Gibson, Ludlam, Eadie.
Replacements: Fish, Davis, Ford-Robinson, Coles, Wood, Davies, Tuitavake, Collins.
Timisoara Saracens: Simionescu; Zaharia, Popa, Umaga, Manumua; Samoa, Rupanu; Taupaki, Radoi (c), Pungea; Lazar, Iftimiciuc; Sabau, Rus, Tatarus.
Replacements: Capatina, Militaru, Halalilo, Stewart, Whitehurst, Neculau, Moala, Shennan.