Brandon Best could be set for a significant spell on the sidelines.
According to the Newcastle Herald, the star Knights centre suffered a hamstring injury in training this week.
The NSW hopeful will reportedly be out for "a couple of months", which would rule him out of all three Origin matches.
Meanwhile, the Sydney Morning Herald has forecast that he will be unavailable for the first two games of the series.
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Best has previously struggled with hamstring injuries, suffering several strains last season.
He was initially named in the Knights' team list for their Friday evening clash with the Eels but is a late omission, with Dylan Lucas taking over from him in the centres.
The 23-year-old has been steady so far this campaign, scoring three tries and setting up two in nine matches.
His injury is unfortunate timing for Newcastle, with winger Greg Marzhew ruled out for a month with a knee injury just days ago.
Knights confirmed team list vs. Eels
1. Kalyn Ponga
2. James Schiller
3. Dane Gagai
11. Dylan Lucas
5. Fletcher Hunt
6. Fletcher Sharpe
19. Tyson Gamble
8. Jacob Saifiti
9. Phoenix Crossland
10. Tyson Frizell
12. Kai Pearce-Paul
16. Thomas Cant
13. Adam Elliott
14. Jayden Brailey
15. Mat Croker
17. Brodie Jones
18. Jack Hetherington
22. Paul Bryan