Lucas missed Saturday's 26-6 loss to Gold Coast at CBUS Super Stadium along with fellow forwards Leo Thompson (knee) and Kai Pearce-Paul (suspended) after sustaining the injury at training earlier in the week.
Those absences opened the door for Jermaine McEwen to make his NRL debut against the Titans but O'Brien isn't sure any of the missing trio will be back for the round-five clash with the Bulldogs, despite having a bye next weekend.
"Dyl Lucas will be out for about six weeks," O'Brien said. "It's a pretty significant hamstring."
"I couldn't completely rule Leo out, but unlikely, and then Kai's got one more game to serve.
"We certainly missed the two back rows and Leo, but I thought the young debutant was great. He had some really good touches."
Regardless of who is and isn't available, Knights captain Kalyn Ponga fully expects the bye weekend to be far from a break for his team after a disappointing night on the Gold Coast.
The Titans ran in four tries to one despite the Knights having the edge in the territorial battle with ill-discipline and costly errors leaving O'Brien's team with plenty to ponder heading into next week.
"It'll be tough to let that one sit for two weeks," Ponga said.
"Definitely you want to get back into it, get back to work and put in a performance that we know we've got but take our lessons.
"It's a bye but we'll still probably work and we'll be right, just learn from this one."
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