NSW and Newcastle centre Bradman Best is out of game one of the State of Origin series, adding to the Blues' injury devastation.
Best damaged a hamstring in Newcastle's 28-22 win over Gold Coast on Saturday.
The 22-year-old scored two tries in his Origin debut last year and was integral to NSW's 24-10 win in game three.
The Blues have already lost key players Nathan Cleary, Tom Trbojevic and Cameron Murray to injury for the duration of the series.
Best is the latest to join the casualty ward for at least the series opener on June 5 in Sydney.
"Bradman has been diagnosed with a grade two hamstring injury and he will miss at least four weeks," Knights football boss Peter Parr told AAP.
"That would put him out of Origin 1. He played exceptionally well on his debut and our expectation at the Knights was that he would get picked for NSW.
"I spoke to him this afternoon and his attention had already turned to getting his rehab right.
"He is obviously disappointed but he has accepted that it is what it is. My conversation with him was all about his recovery and making sure he got back as quick as he could."
Best's absence is a blow but the Blues have options.
Canterbury skipper Stephen Crichton plays both left and right centre, which means coach Michael Maguire can pick the best of the other centres no matter what side of field they prefer.
South Sydney talisman Latrell Mitchell, Cronulla weapon Jesse Ramien, Brisbane pocket rocket Kotoni Staggs and powerful Joseph Sua'alii from the Sydney Roosters are all contenders.
Best has come a long way in multiple facets since bursting onto the scene, with his maturity and approach to training and recovery a plus.
"I think he has got a really good understanding now of the work required to be a top shelf NRL player," Parr said.
"Since he has learnt that, he has played particularly well. His off-field professionalism has improved out of sight over the last 18 months and that will stand him in good stead for this test."
The Knights have a bye in round 12 after four consecutive wins and have options to replace Best.
"We could move Enari Tuala into the centres and potentially Tom Jenkins onto the wing," Parr said.
"We have also got Dylan Lucas, who has filled in quite well at centre on a couple of occasions, including the second-half on the weekend, and he would be under consideration as well particularly now that Tyson Frizell is back."
