Orgeron said it was a non-contact injury that Edwards-Helaire suffered Tuesday, but the extent of the injury isn't clear yet as the medical staff continues to perform tests.
"We're going to know more by the end of the week," Orgeron said.
The No. 1-ranked Tigers play No. 4 Oklahoma in the College Football Playoff semifinal game at the Chick-fil-A Peach Bowl on Dec. 28 in Atlanta.
Edwards-Helaire was an All-SEC first-team selection this season, rushing for 1,290 yards and 16 touchdowns. The 5-foot-8 junior from Baton Rouge also caught 50 passes for 399 yards and a touchdown.
Quarterback Joe Burrow, who took home the Heisman Trophy last week, is the team's second-leading rusher with 289 yards on the ground. Freshman running back Tyrion Davis-Price, a former four-star recruit, is third on the team with 279 yards and six touchdowns rushing.
Orgeron said it will be a matter of the next man stepping up if Edwards-Helaire is unavailable against Oklahoma, but added that, "I'm not sure that Clyde can't play or can play yet."