Brailey played 61 minutes of the win over the Warriors - the third of the year for the Knights, who have also had a draw and sit in the top eight after the game - before leaving the field injured.
The dummy half has struggled enormously with injury in recent seasons, and the latest set back will be a big blow to the Knights as they attempt to firm on their position within the NRL's top eight.
O'Brien suggested Brailey could be looking at a four to week stint on the sidelines.
"They are talking about a meniscus. Obviously he will go through scans," O'Brien said.
"I don't know how long they are - four to six weeks or something like that, but yet to be confirmed."
The Knights, who used Phoenix Crossland in the halves against the Warriors, will welcome back Tyson Gamble from his mandatory 11-day standown after a concussion last weekend for next week's Saturday game against back-to-back defending premiers the Penrith Panthers.
O'Brien said it will allow him to use both Crossland and Kurt Mann, who also returned last night, in a dummy half rotation. The Knights, of course, allowed Chris Randall to move to the Gold Coast Titans prior to the season, leaving them with no first-grade equipped back up dummy half.
"Having Tyson Gamble come back will allow Phoenix and Kurt to rotate through that nine spot. It'll take two of them to cover Brails in the middle," O'Brien added.
O'Brien said he was impressed with Crossland's performance in the starting side on Sunday evening, comparing it to another game he started in seasons gone by against the Manly Sea Eagles.
"Really happy," O'Brien said.
"A couple of years ago he played against Manly, and a very similar job. He kicked us into good positions and it's a credit Phoenix.
"He has obviously come through the system here at the Knights. His preferred position in the juniors was in the halves, but I've thrown him at 13 and 9 and wherever I've needed to put him, but he never whinges and just gets on with it. He is a good kid."
The X-Factor play remaining for the Knights will be the return of Kalyn Ponga, who the club have suggested could be back as soon as Round 8.
O'Brien admitted he was unsure how he would use the star fullback turned five-eighth though upon his return to first-grade, with Ponga not playing since Round 2 and since flying to Canada for specialist treatment after yet another concussion.