It is the second year in a row in which Yeldon has failed to finish the season healthy. He missed the final three games of his rookie campaign because of a knee injury.
Yeldon is the Jaguars' leading rusher (465 yards) but has run for only one touchdown and is averaging just 3.6 yards per carry.
He does play a vital role in pass protection, though, so the Jaguars will miss his absence there, too.
Yeldon was hurt on his second carry in the victory over the Titans. To replace Yeldon on the roster, the Jaguars claimed running back Daryl Richardson, who was waived by Pittsburgh on Sunday.
The Jaguars (3-12) finish the season Sunday at Indianapolis (7-8).
Chris Ivory is expected to handle most of the work against the Colts. But Ivory re-injured a strained right hamstring against the Titans. It's the same injury that caused him to miss two games earlier this month.
The Associated Press contributed to this report.