The 32-year-old hooker has a problem with a disc that looks certain to require surgery and keep him out until at least April.
It is a huge blow for the reigning Celtic League champions as Williams is the third forward the team have lost this season after Lions and Wales duo Ryan Jones (shoulder) and Brent Cockbain (hamstring) were ruled out for the season.
"It is not great news for Barry or the Ospreys," said rugby manager Derwyn Jones.
"The season has been a difficult one for the region but Barry has led from the front and not once taken a step back.
"At this stage it looks as if he will be out until the end of April, but until he has the consultation we can't be more precise."