Kangaroos ruckman Todd Goldstein, Will Phillips and Miller Bergman have all been dropped for Sunday's tough trip to face the reigning premiers at GMHBA Stadium.
Former captain Jack Ziebell is out of the starting 22 to serve as the substitute, while Liam Shiels (calf/plantaris) is injured.
Tristan Xerri, Lachie Young and Flynn Perez are back after extended stints out of the side and son-of-a-gun Cooper Harvey will make his debut.
Goldstein has been left out in favour of Xerri for the second time this season, having been overlooked in round one.
Xerri required ankle surgery after he was injured in that match but has fought his way back to make his second senior appearance of the year against the Cats.
Tuohy will pass legendary ruckman Jim Stynes' mark for most AFL/VFL games played by an Irishman when he lines up for the 265th time.
O'Connor is back after a week out with an adductor issue and emerging first-year player Mullin will make his third senior appearance.
Jed Bews (knee) and Jake Kolodjashnij (adductor) are out injured, while veteran wingman Isaac Smith has been managed.
Star forward Jeremy Cameron (concussion) remains sidelined but got through training on Thursday and is expected to be available next week.
Essendon look set to make Dylan Shiel their substitute again for their crunch clash with top-eight rivals Adelaide at Marvel Stadium.
The Crows have promoted last week's sub Lachlan Sholl in place of Jordan Butts (concussion).
Fremantle have lost star utility Nat Fyfe to a foot injury and promoted Neil Erasmus to their 22 for a high-stakes meeting with fellow finals hopefuls Carlton at Optus Stadium.
Karl Worner will debut as the Dockers' substitute.
Carlton will again be without injured ruck duo Tom De Koning and Marc Pittonet (both knee) and have recalled forward Matthew Cottrell.
Ed Curnow and last week's substitute George Hewett have both been named as emergencies.
