Heinrich Brüssow and Tom Collins will both return from injury in Saints' game at Timisoara Saracens on Saturday (kick-off 12.30pm GMT).
Brüssow has not played since the defeat to Saracens on September 15, making just three appearances this season due to concussion.
Collins has not featured since fracturing his cheekbone in the Premiership Rugby Cup clash with Gloucester at Kingsholm on November 9.
But both players are fit to start in this weekend's Challenge Cup game in Romania.
Luther Burrell will skipper Saints after scoring twice in the 48-14 win against the Dragons at Franklin's Gardens last Saturday.
Academy graduate Devante Onojaife will start a first-team game for the first time, with the back row forward adding to his three previous appearances off the bench.
James Grayson, who recently signed his first senior contract at Saints, replaces Dan Biggar, who will be rested alongside fellow internationals Dylan Hartley and Courtney Lawes.
Boss Chris Boyd has named a youthful bench that contains the likes of Alex Moon, Paddy Ryan and lock Alex Coles.
Saints: Tuala; Sleightholme, Dingwall, Burrell (c), Collins; Grayson, Mitchell; Van Wyk, Marshall, Hill; Ribbans, Ratuniyarawa; Onojaife, Brüssow, Eadie.
Replacements: Fish, Davis, Painter, Moon, Coles, Ryan, Davies, Hutchinson.