Darcy Moore and Nathan Kreuger are among the players who have trained away from the main group as a precaution in the past week.
Jordan De Goey was ill and missed last round's win over St Kilda, but is set to return against the Bombers at the MCG.
Magpies coach Craig McRae said the club had adopted a cautious approach to illness after being stung last season.
"We're a little bit gun-shy from last year," McRae said this week.
"Illness went through the place last year for about three weeks and we're a little bit scared of that.
"So anyone that's got a little sniffle, they're not coming in."
Moore and Kreuger have both been cleared to play, with the latter returning for his first game of the season after undergoing a right shoulder reconstruction in January.
The versatile tall could line up in several roles, with the injury-hit Pies looking for cover at both ends of the ground.
Kreuger could also assist key defender Billy Frampton in a ruck battle with Essendon duo Sam Draper and Andrew Phillips, with the Pies' regular ruckmen sidelined.
Darcy Cameron (knee), Mason Cox (spleen) and Aiden Begg (back) are all unavailable, as is key forward Dan McStay (finger) and defender Nathan Murphy (concussion).
Magpies wingman Steele Sidebottom backed Frampton and Kreuger to stand up against the physical Bombers ruck pairing.
"We've clearly had our ruckmen go down but Billy's the kind of guy where you put a role in front of him and he's happy to do it," Sidebottom told SEN.
"He's got that little bit of mongrel in him as well, which is nice for a guy who is going into the ruck.
"Kreuger is a similar type of player. He'll come in and throw himself around whether he has to play forward or back.
"But they're both guys who will have a crack for us."
It is just the second time in 28 Anzac Day meetings that Collingwood and Essendon have both entered as top-four sides.
Both boast 4-1 records after impressive starts to the season and the contest is expected to draw more than 90,000 fans to the MCG.
"It's no bigger than any other game - that's the reality in terms of four points - but the occasion itself, clearly there's a lot to embrace," McRae said.
"The day itself is such a great occasion and we're going to step right into it.
"We're not going to shy away from the big crowd."
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