The ACT Brumbies back-rower left last round's victory over the Highlanders in the first half and later complained of shoulder soreness.
After undertaking scans, the club confirmed on Friday that he would miss between four to six weeks.
It's a blow for their top tryscorer, who was gunning for a Wallabies recall after suffering back stress fractures, which meant he missed a large chunk of last year.
The injury comes as fellow back-rower Rob Valetini prepares to meet his brother Kemu, when the Brumbies host the Fijian Drua on Saturday night.
Family members are expected to fly in from Melbourne to the nation's capital for the occasion after Kemu missed their round-five clash, a shock 42-27 Drua triumph in Ba.
That result also meant Rob couldn't cap off his 100th Super appearance with a victory and, with their rematch looming, is looking to gain a slice of revenge.
"We have played each other a couple of times now. But that feeling doesn't go away. It's always unreal to see the sibling on the other side at this level," the veteran Wallabies forward, with Fijian descent, said.
"Hopefully, we can both be on at the same time and have a few minutes against each other.
"Just knowing our parents are watching on from the stands will be really nice."
The Brumbies will need to pick up a victory to keep their top-two aspirations alive as they sit three points behind the second-placed Chiefs (27) on a congested ladder.
They will take some confidence from a grinding 14-10 victory in Dunedin last Friday, which coach Stephen Larkham branded as their best defensive performance of the year.
"They have got that razzle dazzle about them. They're big athletes, and one-on-one, they're quite hard to tackle and defend against," Rob said of the Drua.
"We talked about our defence being more aggressive ... that will be the main focus for us."
Despite Cale's absence, the home side will be boosted by Wallabies fullback Tom Wright, who returns from an ACL tear he suffered last August against South Africa.
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