Hayden, a late withdrawal from the side that lost to the Western Bulldogs in round one, will play his first game for the season after overcoming a hamstring injury.
Duffield, who was omitted following the loss to Essendon in round two, joins him after a polished performance for South Fremantle in the WAFL.
Clayton Hinkley has been omitted while Greg Broughton will miss one week with an ankle injury.
Football administration manager Brent Dawkins said Hayden's return would bolster the defence for the Docklands clash.
"[It's] really exciting for Roger to get back in the side for his first game for the year," Dawkins said.
"He was an important part of our backline last year when he was playing and his run will be an asset this weekend."
Duffield was one of Fremantle's best in round one after an interrupted pre-season.
The utility broke his wrist at the end of January, limiting his touch work, but he was back in form against Subiaco last Thursday night.
"He played really well, played on the ball and had a great game," Dawkins said.
"He managed to pick up a stack of possessions and ran really hard. So [it's] straight back into the team for Paul."
Draftees Stephen Hill and Nic Suban have held their spots after encouraging games against Adelaide on Sunday.
Dawkins said the opportunity for the 18-year-old pair to travel was valuable.
"They're exciting young kids to have in the side, and they're learning all the time, whether we're playing at home or away," he said.
"Just getting on a plane every second week and learning the rigours of travel brings them along."
Rookie elevation Matt de Boer was named as an emergency for the second week in a row, alongside Hinkley and Ryan Murphy.
THE TEAM
B: Roger Hayden (43), Michael Johnson (37), Chris Tarrant (20)
HB: Josh Head (42), Antoni Grover (14), Steven Dodd (25)
C: Rhys Palmer (10), Paul Hasleby (4), Garrick Ibbotson (5)
HF: Daniel Gilmore (27), Luke McPharlin (18), Byron Schammer (3)
F: Brett Peake (7), Matthew Pavlich (29), Kepler Bradley (26)
Ruck: Aaron Sandilands (31), Ryan Crowley (15), David Mundy (16)
I/C: Dean Solomon (6), Stephen Hill (32), Nic Suban (8), Paul Duffield (41)
Emg: Matt de Boer (40), Clayton Hinkley (19), Ryan Murphy (28)
In: Hayden, Duffield
Out: Greg Broughton (ankle), Clayton Hinkley
Milestone: Antoni Grover to play his 150th game
FORECAST (Melbourne)
Fine. Min: 13 Max: 20
Partly cloudy. Isolated showers in the afternoon and evening. Winds south-westerly averaging up to 25 km/h.
BROADCAST DETAILS
TV
FOX Sports 1
Live nationally 5pm AWST
Channel 10
Live at 5pm AWST
Radio
Perth 6PR and ABC
Melbourne 3AW and Triple M
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