Best was injured in the 28-22 win over Gold Coast on Saturday. The 22-year-old scored two tries in his State of Origin debut last year and was integral to the 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 and can ill-afford to be without Best.
The Knights players have time off ahead of the bye next week and Best had planned to visit family in Logan. Instead he will have scans and begin rehab.
"Bradman will have scans in Newcastle on Monday and we will wait on the results from there," Knights football boss Peter Parr told AAP.
"We probably weren't expecting him to be right for our next game anyway because our expectation would be that he would play for NSW but we will wait and see what the scans say."
The Knights have won all four games since star fullback Kalyn Ponga was ruled out for up to 12 weeks with a Lisfranc injury to his foot.
His replacement David Armstrong has been a revelation, five tries in four games including a hat-trick against the Titans.
David Armstrong streaks away for his third try in the Knights' win over Gold Coast. (Dave Hunt/AAP PHOTOS)
Ponga has moved off a trolley and into a moon boot and is set to start putting weight on his foot as his rehabilitation ramps up.
"My understanding is that the 12 weeks is accurate," Parr said of Ponga's time on the sidelines.
"I reckon we have gone half of his absence without losing because in that 12 weeks there are three byes and our expectation is that he would have been somewhere in the Queensland 17 as well."
When Ponga was injured the Knights had Fletcher Sharpe in the wings to replace him. Sharpe wasn't available due to a hamstring injury and Armstrong stepped into the breach.
Coach Adam O'Brien said the 23-year-old had been rewarded for not holding back and putting himself in the game.
"Stuff happens around him because he goes to the game," O'Brien said.
"He got rewards for pushing up around the forwards at the start of the game to get him those tries.
"I reckon the bye has come at the right time for Dave. It has been a steep mountain for him the last month so it will be good for him to have a rest and go again."
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