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Jake Stringer is sidelined with a hamstring injury, dealing Essendon a major blow for their opening AFL clash against arch-rivals Hawthorn.
The Bombers reported last month that Stringer had hamstring tightness, which ruled him out of their two pre-season hitouts.
They were hopeful he would be ready for Sunday's clash at the MCG, but he has not recovered in time.
Essendon have a number of injury concerns this week, with former captain Dyson Heppell (foot), Jye Caldwell (ankle) and Ben Hobbs (calf) all needing fitness tests.
But Stringer is a major blow, given his proven ability to turn a game and the need for the Bombers to start the season well against the Hawks under new coach Brad Scott.
Stringer was restricted to 15 games last season because of groin and hamstring issues.
"Our performance team have put together a comprehensive plan with Jake to get him back to his best post-injury," said Bombers performance manager Daniel McPherson.
"He participated in a strong session on Saturday, and we want to make sure he has block of full training with the main group before he is available for selection.
"It's a long season ahead and we want to ensure Jake is fully ready to go when he returns to play, so we won't be rushing him back."
Heppell hurt his foot against the Suns in the pre-season, while Caldwell sprained his ankle in their loss to St Kilda.
"(Jye) has been really diligent with his rehabilitation which has enabled him to return to running in a short amount of time," McPherson said.
"He has satisfied all the milestones set by the high-performance team and will reintegrate into the main group this week."
Likewise, the Bombers are impressed with Hobbs' progress back from a calf strain and also hope Heppell will be available.
Matt Guelfi and Kyle Langford played well in a VFL practice match on the weekend to boost their selections hopes for round one.