Isaac left the floor in a wheelchair Sunday after sustaining a non-contact injury late in Orlando's blowout win over the Sacramento Kings.
The 6-foot-11 forward underwent an MRI that revealed the extent of his injury following the contest.
Isaac suffered a severe sprain in the same leg during a New Year's Day contest against the Washington Wizards. That issue had sidelined him until he returned to the Magic's lineup for Friday's game against the Brooklyn Nets.
The 22-year-old has averaged 12.1 points, 6.9 rebounds, 2.4 blocks, and 1.5 steals this season.
Isaac garnered national attention when he stood for the national anthem on Friday while his teammates, coaches, and the opposing Brooklyn Nets all opted to kneel.
"I believe that Black Lives Matter. A lot went into my decision, and part of it is that, first off, it's my thought that kneeling while wearing a Black Lives Matter T-shirt don't go hand in hand with supporting Black lives," Isaac said of his decision.