ESSENDON is set to be without gun small forward Orazio Fantasia for Wednesday's Anzac Day clash with Collingwood as he struggles to overcome a calf injury.

Fantasia, who returned to the Bombers' line-up in round three after pre-season knee surgery, ran laps at the club's main session on Sunday and appears likely to miss the MCG clash.

Coach John Worsfold confirmed on Monday morning that the 22-year-old is in serious doubt.

"He's pushing to try and get up, but at this stage it looks like he'll probably miss," Worsfold told SEN.

"We will obviously assess him again tomorrow and just get a feel for where he's at and then it comes down to the medical call in association with how Fantasia is feeling. At this stage he's unlikely."

The Bombers won't take risks with the talented forward, who kicked 39 goals last season and became one of their best players with his speed and class in attack.

The Dons play again on Sunday against Melbourne, meaning they have a four-day turnaround between games, but Worsfold said that wouldn't be factored into their planning for Fantasia.

"We really just look at if they're available for Wednesday and treat this really in isolation and treat this like any other game, disregarding what’s happening in the next week," he said.

"So if they're available and in our best team, they'll be selected and then we'll deal with the outcome of that on Thursday.

"You can do some planning and then players pull up sore and that flips everything on its head."

Jackson Merrett could come into contention as a replacement for Fantasia in what would be his first senior game since 2016.