Wallabies Will Genia, Dane Haylett-Petty and Adam Coleman have all been ruled out for the Melbourne Rebels, in a blow to their hopes of a season-defining win over the Highlanders.
The key players all failed fitness tests and will miss Saturday's Super Rugby match in Dunedin against what will also be a weakened home side.
With little at stake, the Highlanders have rested a number of key players, offering a glimmer of light to the desperate Rebels.
Dave Wessels' side must win to guarantee a first finals appearance.
They'll need to do so without fullback Haylett-Petty (hyperextended knee) and halfback Genia (broken arm), who both trained with the team on Wednesday but were deemed unready.
Coleman (adductor strain) was always unlikely to feature after missing training.
His absence is compounded by a shoulder injury to English international lock Geoff Parling, forcing the Rebels to field a second-choice second row.
Matt Philip is joined by fellow-rookie Ross Haylett-Petty, with the latter making his first start since April.
Props Tetera Faulkner and Jermaine Ainsley have paid for a substandard scrummaging return in last week's 37-23 loss to the Queensland Reds.
The pair are demoted to the bench in a straight swap with Fereti Sa'aga and Sam Talakai.
Jack Maddocks shifts to fullback for Dane Haylett-Petty and Sefa Naivalu moves off the bench to the right wing.
Forwards Sam Jeffries and Lopeti Timani both return on the bench.
All Blacks backs Ben and Aaron Smith will both be missing from the Highlanders backline, along with in-form centre Rob Thompson.
Loose forwards Luke Whitelock and Dillon Hunt are missing from their regular starting pack, along with lock Tom Franklin.
With the Highlanders guaranteed a finals spot, coach Aaron Mauger has handed a Super Rugby debut to centre Thomas Umaga-Jensen while it is the first start for fullback Josh Ioane.
Rebels five-eighth Reece Hodge has urged his side not to get caught up in what's at stake, as he believes happened in losses to the Waratahs and Reds.
"If you try to think too far ahead, you're not focusing on what you've got to do to get there," Hodge said.
"We can't stray away from the fact that we haven't won the last two games when we really wanted to, having put ourselves in such a great position to make the finals."