In other notable round 11 team news, Essendon recalled Ben McKay for their 'Dreamtime at the G' clash with Richmond, while Carlton lost All-Australian defender Jacob Weitering due to calf tightness.
The Dockers have the chance to post a new club-record 10th straight win when they face Ross Lyon's St Kilda in Perth on Friday night.
Already missing concussed midfielder Hayden Young, Fremantle were dealt another big blow when Serong was cut down by a calf strain, with early whispers suggesting he will miss two to three weeks.
"Caleb had some calf awareness following the Essendon game and scans have now revealed a strain," Fremantle's general football manager Joe Brierty said.
"We will monitor Caleb's functionality in the coming days and provide an update next week."
Serong has been replaced by Corey Wagner, while the Saints brought in Mason Wood for Jack Higgins (knee).
Collingwood veteran Scott Pendlebury returns for his record 433rd AFL appearance, and he has been joined in the side by fellow stars Darcy Moore, Patrick Lipinski and Darcy Cameron.
West Coast have made just the one change, bringing in 2024 first-round draft pick Bo Allan for Jack Hutchinson (hamstring), meaning No.4 draft pick Cooper Duff-Tytler will spend a second straight week on the outer.
Essendon have recalled Jade Gresham, Tom Edwards and Matt Guelfi alongside McKay for their 'Dreamtime' clash, while Richmond brought in Mykelti Lefau and Jasper Alger for Campbell Gray (hamstring) and Liam Fawcett (omitted).
The Brisbane Lions are still without veteran Dayne Zorko, who was a late out last week with soreness, and they have also lost Ryan Lester after he injured his calf at training on Thursday.
Premiership forward Ty Gallop is back for Sunday's clash against GWS, with the Giants hopeful defender Jack Buckley will return from hamstring soreness.
GWS utility Ryan Angwin, who fractured his knuckle against West Coast, is set to spend three weeks on the sidelines.
Ladder leaders Sydney have called up Caiden Cleary and Tom Hanily for Saturday's GMHBA Stadium meeting with Geelong, who go in unchanged.
Gold Coast have welcomed back Ben Long and Sam Clohesy for Saturday's clash with North Melbourne at Marvel Stadium, but Lachie Weller (hamstring) and Will Graham (concussion) have been ruled out.
Along with losing Weitering following last week's win over the Western Bulldogs, Carlton will also be without Ollie Hollands (ankle) and Zac Williams (managed) against the Power in Adelaide.
Port have lost Lachie Jones to concussion and have handed recalls to Todd Marshall, Josh Lai and Jacob Wehr.
Bulldogs veteran Adam Treloar has been named as part of the extended squad for Sunday's meeting with Melbourne, but Tim English (concussed) remains sidelined.
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