Best sustained a calf injury in training and was confirmed to be out of the Knights’ Magic Round clash with the Titans on Sunday.
Now the Blues’ worst fears have been confirmed with the centre set to be sidelined for several weeks.
Initially assessments suggested Best would be absent for game one, but he is now set to miss the entire series.
And he could be joined in his absence by Ponga.
According to Nine News the fullback sat out the Knights’ final training session before Magic Round and the Maroons are now sweating on his fitness.
It is a big blow for the team after Tom Dearden suffered a brutal injury last week.
Ponga was tipped to replace the Cowboys star but faces a race to be fit in time for game one.
However the Blues’ woes are arguably even greater, with their other preferred centre Latrell Mitchell also a big doubt.
The Rabbitohs man missed last week’s game with a back problem and had to be taken off in their defeat to the Dolphins on Friday.
Bradman Best injury, Kayln Ponga fitness, State of Origin blues, Latrell Mitchell back problem, Knights Magic Round Titans, Tom Dearden injury