Jake had only returned to the Sea Eagles' side for their clash with the Canberra Raiders in Round 12, making a last ditch effort to recover for State of Origin.
The Sea Eagles revelaed on Tuesday though that the lock forward, who returned from injury two weeks ahead of schedule, has now suffered a torn calf and is expected to spend up to six weeks on the sideline.
His youngest brother Ben has also re-injured his hamstring with scans confirming it to be a tear and while the Sea Eagles didn't put a return timeline on his availability, the club said he would be out for an "extended period" suggesting he won't be available to suit up for the Sea Eagles during the State of Origin period.
It means the duo both need to be replaced for this Sunday afternoon's clash with the Newcastle Knights in the Hunter, before Manly have a bye in Round 14.
In slightly better news for the club - particularly for their forward depth - Josh Aloiai is expected to return after that bye after he dislocated his shoulder during Round 11.