Melbourne's hopes of a record fourth consecutive win when they face the Crusaders have been dealt a heavy blow with Lukhan Salakaia-Loto sidelined after undergoing foot surgery.
The injury threatens his entire Super Rugby Pacific campaign.
Salakaia-Loto and five-eighth Carter Gordon are the only Rebels to have played every minute of every match with coach Kevin Foote conceding the superstar lock will be sorely missed for Friday's big clash in Christchurch.
Currently sitting fourth, the Rebels are looking to win four successive games for the first time in their Super history, while expecting the fallen Crusaders to provide a tough challenge on their home turf.
Salakaia-Loto fractured his foot late in their round-eight win over the Highlanders and had a pin inserted last week.
"He's been huge, Lukhan, not only as a player, his leadership has been phenomenal," Foote said of the 27-year-old.
"He puts in a massive load ... just his whole work ethic is huge."
Melbourne have named Josh Canham as their second-row replacement while Wallabies backrower Rob Leota will make his return from a calf injury through the bench.
Brumbies skipper Allan Alaalatoa is available to face the unbeaten Hurricanes in Canberra on Saturday afternoon.
Rupturing his Achilles last year, it's prop Alaalatoa's first match of the season with his third-placed side looking to rebound from a disappointing loss to the Blues.
In other changes, openside flanker Rory Scott will start for the first time this year while outside centre Len Ikitau and reserve back Andy Muirhead return from round-four injuries.
The timely return of centre Josh Flook is one of three changes to Queensland's starting side for Saturday night's clash against the Blues at Suncorp Stadium.
The Reds will wear their unique khaki Anzac jersey in Super Rugby Pacific's first Anzac Weekend Round, where all five Australian sides are pitted against New Zealand opponents.
Flook replaces outside centre Jordan Petaia, who suffered a season-ending shoulder injury, while lock Angus Blyth comes in for Cormac Daly, who is sidelined with injury niggles from the 31-0 victory over the Highlanders.
Pacey 2023 Junior Wallabies winger Tim Ryan will make his first start with coach Les Kiss resting regular winger Mac Grealy.
Off the bench, lock-backrower Connor Vest is in line for his first appearance of the year while Floyd Aubrey, the Indigenous winger-fullback who began his journey in Murgon, is ready for a potential debut after a fine performance for his club GPS last weekend.
The Waratahs have recalled axed winger Mark Nawaqanitawase for Friday's Allianz Stadium clash with the Chiefs while coach Darren Coleman has also shifted his forward pack around, dropping Jed Holloway and Langi Gleeson to the reserves.
The Western Force travel to Dunedin to face the Highlanders on Saturday afternoon with captain Jeremy Williams, who has missed the past three games with injury, the reserve lock.
Fellow lock Izack Rodda has been elevated into the starting XV for ex-Highlander Tom Franklin (head injury protocols) after a successful return from a quad issue.