Coach Luke Beveridge has been forced into a reshuffle for Saturday's Marvel Stadium contest, which pits the seventh-placed Bulldogs (8-6) against one of several sides in the chasing pack.
Liam Jones (broken arm) and Tim O'Brien (hamstring) have joined running pair Jason Johannisen and Ed Richards (both hamstring) on the sidelines.
O'Donnell and Gardner have put their hands up at VFL level in recent weeks.
"James O'Donnell has impressed early with some of his aerial stuff, and Gardy was (seventh in the) best-and-fairest for us last year," Bulldogs teammate Cody Weightman said.
"We'll have full confidence in whoever comes in to play that role but replacing a guy like Jonesy is going to be hard when he's had a great year."
The inclusion of Gardner and O'Donnell means Beveridge is likely to leave Aaron Naughton stationed in attack after the leading goalkicker moved back during the round-14 win over North Melbourne.
"My personal hope is that he's forward with me but if (the backline) is where he needs to be then I'm sure he'll play an effective role," small forward Weightman said.
The Bulldogs have also handed mid-season recruit Caleb Poulter his first senior game for the club.
Fremantle (7-7, 11th) have regained wingman James Aish three weeks after he suffered concussion from the bump that led to Richmond player Rhyan Mansell's suspension.
Geelong captain Patrick Dangerfield and tall defender Esava Ratugolea are back from injury, as expected, for their side's trip to face Sydney at the SCG on Friday night.
The Swans' hopes of causing an upset were dealt a blow when gun midfielder Chad Warner was ruled out with a "slight tear" in a calf muscle, replaced by Will Hayward.
Veteran forward Lance Franklin (knee) is still out of action.
Tom Mitchell has been named for Collingwood's clash with Gold Coast on Saturday night despite concerns over a neck injury, with the inside midfielder also battling a sore back earlier in the season.
All-Australian defender Brayden Maynard has also been cleared to play after copping a knock to his left shoulder last week and Billy Frampton comes in to face the unchanged Suns.
Adelaide are also unchanged for Saturday's home clash with North Melbourne, who have been bolstered by the return of Luke Davies-Uniacke and Darcy Tucker.
Kangaroos midfielder Hugh Greenwood was dropped for the meeting with one of his former clubs.
Essendon left Nick Bryan out of their 22, naming him on the emergency list for Saturday night's huge clash with Port Adelaide at the MCG.
Dylan Shiel could return from a foot injury as the Bombers' substitute, while the Power have gained potency around goal with the return of Junior Rioli.
Small forward Rioli is back after missing Port's win over Geelong through illness.
Carlton have lost ruckman Marc Pittonet to injury for Sunday's meeting with Hawthorn and recalled out-of-favour utility Jack Silvagni to partner Tom De Koning in the ruck.
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