Essendon's Rhys Unwin and St Kilda's Alex Dodson will make it 24 debutants between the two outfits this AFL season - more than a whole team.
That number illustrates how challenging a year it has been for the two teams, who are an unlikely match-up in the prime-time Friday night slot.
Unwin will be the Bombers' 15th debutant, easily the most for any team this season as they have struggled with a shocking injury run.
Dodson will bring the Saints' newcomers to nine, equal-second with Richmond.
The Bombers and Saints made three changes apiece, with Bombers forward Kyle Langford returning from a quad injury for only his seven game this season.
Saad El-Hawli is the other inclusion as the Bombers lost captain Zach Merrett to hand surgery and Archie May to a sprained ankle.
Typical of the Bombers' dire fortunes this season, Dylan Shiel was suspended after an unusual tribunal case where he was penalised for hurting his own teammate.
Dodson, a 203cm ruckman, demanded selection after 25 disposals and 41 hitouts last weekend in the VFL.
Lance Collard and Toby Travaglia will also return, while Hunter Clark is out because of a knee injury. Max Heath and Liam Henry were dropped.
While the Saints will start favourites as they aim to continue their strong finish to the season with a fourth-straight win, Essendon are on a 10-game losing streak.
Saints coach Ross Lyon has been in the headlines this week, denying speculation about playing unrest at Moorabbin ahead of the post-season trade period.
