Former Sydney Swan Ed Barlow and first-year rookie Luke Dahlhaus have been named to start on the bench against the Saints along with one of the other six inclusions - Tom Liberatore - and Nathan Djerrkura.
Dahlhaus will play his first game of AFL football while Barlow will play his first since round seven last year, and debut as a Bulldog.
Adam Cooney will return for his first hit-out since round eight while Ben Hudson has been given a reprieve after coach Rodney Eade said he took "his penance" with two weeks in the VFL. Brennan Stack makes up the inclusions for the side.
As reported earlier on Thursday, the Dogs have lost Brian Lake to groin soreness while Ryan Hargrave is out again with his persistent foot problem.
Josh Hill, Jarrad Grant, Mitch Wallis and James Mulligan - after just one game - have been omitted.
"Luke is a young player from Geelong, he's on our rookie list, he's got quite a bit of pace and he's been in very good form," Eade told Bulldogs TV on Thursday night.
"He's on our rookie list at the moment but he's been elevated.
"His form over the past four to five weeks for Williamstown has been terrific and it forced our hand to pick him.
"There wasn't a lot of positives last week but we thought Nathan Djerrkura gave us a bit of lift when he came off the substitute bench in the third quarter.
"Hopefully he can continue that form."
Barlow, 24, is a tough utility who played 26 games for the Swans between 2007 and 2010; 15 of which he kicked goals in.
First-year player Jayden Schofield, who Eade said earlier in the day was in the selection mix, has been named as an emergency along with Wallis and Mulligan.
Eade said the players were geared up for what loomed as a season defining game for the side, which has won just one game in its last seven starts.
"We believe this is a line in the sand game against a great rival so we're looking for a big game from all of our players," Eade said.
"We believe this is a winning squad and we look forward to the game."