Darcy has been in strong form this season, with the 24-year-old now rated as one of the best ruckmen in the competition.
The 203cm, 110kg Darcy tallied 38 hit-outs, 21 disposals, and nine clearances in last week's eight-point win over Port Adelaide.
That performance came against a makeshift Port ruck duo of Charlie Dixon and Jeremy Finlayson, and Darcy will have a much tougher task against Paddy Ryder and Rowan Marshall.
The powerful Saints ruck duo played a key role in helping St Kilda win the midfield battle in last week's upset 15-point win over Carlton.
Serong, who fed off Darcy's silver-spoon service last week to help Fremantle win the clearances 47-30 against Port, is confident the ruckman will produce the goods again.
"You don't have too many teams in the comp that have two elite ruckmen like the Saints do. It's a different challenge but I feel like Sean's up to it," Serong said.
"They've both been in some really good form, especially Ryder at centre bounces. He's a really good ruckman and gives their midfield first look a lot of the time.
"You see him when (Darcy) comes up against the best ruckmen in the comp, he never shies away from the challenge and he's always there on the front foot getting ready to go."
Fremantle named Matt Taberner despite the spearhead being subbed out of the win over Port with a hamstring concern.
The Saints lost Dougal Howard (knee) and Hunter Clark (face) to injury, paving the way for defender Darragh Joyce to be named for his first AFL match since round two.
Serong will notch his 50-game AFL milestone against the Saints, with the No.8 pick from the 2019 national draft rated as one of the league's brightest young talents.
The 21-year-old has developed a knack for booting outrageous goals, as evidenced by his checkside banana from the pocket off his left boot last week.
It followed on from the checkside banana that won him the goal of the year in 2021.
"I think sometimes there's a bit of naivety to back yourself on the left, sometimes I probably should straighten up on my right," Serong said.
"I work hard on both feet and I hope in the future it can be a real strength of mine, where I can go both ways."
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