The Sharks confirmed on Friday that the 21-year-old lock underwent a scan, which revealed a serious anterior cruciate ligament injury.
Du Toit will undergo surgery and will be out for the remainder of the year.
The Bok lock was named in the Sharks starting XV to play the Reds on Saturday, but on Thursday took a blow to the knee in the morning session.
He was later replaced by Stephan Lewies, who will make his first Super Rugby start against the Reds in Durban on Saturday – after playing off the bench in the three previous games this year.
Sharks Director of Rugby Jake White described Du Toit’s loss as a “big disappointment” and his sentiments will be shared by Bok coach Heyneke Meyer – who has repeatedly gone public with his admiration for the young second row forward.