The 26-year-old was subbed out of the Round 2 win over the Bulldogs with back spasms and, despite a number of treatments, has since been unable to increase his training loads, with the club confirming on Thursday he will now be given an extended period to recover.
"Oscar worked as hard as anyone over the summer to earn a spot in our 22 for the start of the season, that is what makes this news even more disappointing," Carlton Head of Football, Brad Lloyd, said in a club statement.
"For nearly two months we explored every possible avenue available to get Oscar up and going however it wasn’t to be.
"We will now put our focus in making sure Oscar is able to rehabilitate the injury over the remainder of the season."
McDonald has played 87 games in eight seasons at AFL level, arriving at the Blues in 2021 after six years at Melbourne.
The in-form Blues will face Sydney at Marvel Stadium on Friday night, with the first bounce set for 7.50pm (AEST).