Milne was suspended for St Kilda's Anzac Day loss to the Sydney Swans for grabbing at the face of Essendon's Courtenay Dempsey and coach Scott Watters said he knew his conduct had been unacceptable.
Watters said Milne and Arryn Siposs would come into the team against the Magpies as well as small forward Terry Milera, providing the latter could overcome soreness and get through training on Thursday.
"The challenge comes straight back down to Stephen Milne, Nick Dal Santo and probably David Armitage, who has had a good year but was flat last week," the coach said on Thursday.
"That challenge is squarely presented to our leaders this week.
"To win this type of game your leaders need to stand up.
"Those players need to be ready for the challenge."
Watters said Dal Santo, who has averaged 23 disposals this season, was a player the Saints needed to get more out of to challenge the Magpies midfield.
"I expect more from Nick; I think he's been OK," the coach said.
"I probably put him in a bracket of, there's more there and he needs to fight really hard to reach peak performance.
"He's been OK, but he's a player who's going to get some big roles this week."
Milera kicked six goals for Sandringham in the VFL and would likely replace one of the Saints misfiring small forwards this week.
Siposs, who hasn't been able to break back into the team since round two, will get his chance against Collingwood after impressing with 24 possessions at VFL level.
"He played really well last week," Watters said.
"He went back and improved in some areas we wanted him to improve in, but that's going to be an ongoing development process.
"He plays this week and if he performs and delivers in the areas we want him to deliver in, he stays in the side."
With the Saints' small forwards in 'patchy' form, draftee Josh Saunders is likely to get more opportunities in attack after making his debut against the Swans in Wellington.
"We love the way he tackles," Watters said.
"There's a challenge there for our small forwards to step up."
Watters said he was pleased to see Nick Riewoldt acknowledged for his strong start to the season after the captain led with 27 possessions, 13 marks and two goals against the Swans.
"I thought last year his form was outstanding … I probably don't think people gave him the credit for how he performed," Watters said.
"Players get in good form and it's almost 12 months later that everyone picks up on it.
"He's in great form, he's leading really well and he sets a great example to not just our younger players but our senior players as well."
