Luai will not take the field at Kogarah on Saturday after the playmaker experienced delayed concussion symptoms following Sunday's 12-6 loss to Newcastle.
After starting the season strongly, the Tigers have won just two of their eight games since Luai announced his intention to move to the PNG Chiefs in 2028.
The Tigers' form slump has coincided with a heavy injury toll, with centre Taylan May also ruled out of their trip to face the Dragons with a long-standing shoulder issue.
There is some good news for coach Benji Marshall, with lock Alex Twal back after a month out with a knee injury as Jock Madden replaces Luai in the halves.
In Saturday's late kick-off, Brisbane have been forced into mass changes through injury and State of Origin selection as they host Cronulla.
Such is the extent of the Broncos' list of unavailable players, which includes winger Josiah Karapani following his drink-driving charge, only five remain from Michael Maguire's round one team.
Deine Mariner returns on the wing for Maguire's side after being out with acute compartment syndrome in his thigh, while the Broncos are seeking an exemption to allow Xavier Willison (concussion) to be cleared to face the Sharks.
In Sunday's games, Jonah Pezet will replace Mitchell Moses (Origin) in the halves for Parramatta against Manly, who will have a glimpse into their future when Joey Walsh takes the No.6 jersey vacated by the injured Luke Brook.
Fletcher Sharpe slots in at fullback with Kalyn Ponga on Queensland duty for Newcastle, bringing Sandon Smith into the halves as the Knights take on the Dolphins.
The absence of Jack Bostock to Origin duty means Wests Tigers-bound Jake Averillo comes in at centre for Kristian Woolf's side.
On Friday, Penrith will roll out a new-look back row of Scott Sorensen, Luke Garner and Lindsay Smith against South Sydney, with Liam Martin, Isaah Yeo (both Origin) and Isaiah Papali'i (concussion) unavailable.
Jack Cogger replaces NSW's Nathan Cleary at halfback against the Rabbitohs, who have brought Jack Wighton back in to the centres following a broken arm.
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