"I don't want to say too much until we get more tests," Detroit coach Jim Schwartz said after Green Bay's 34-12 win. "But it is something that we'll have to take a hard look at."
Pettigrew was engaged with Packers linebacker Clay Matthews in the second minute of the game when his knee buckled. The injury was severe enough that several Green Bay defenders started waving the Detroit training staff onto the field.
Pettigrew, who caught the winning touchdown pass on the final play of Sunday's 38-37 win over Cleveland, walked off the field with help. He was examined by trainers before being helped back to the locker room.
The Lions announced at halftime that Pettigrew would not return.
Earlier in the game, Lions quarterback Matthew Stafford made his return to the lineup after separating his non-throwing shoulder against the Browns on Sunday.
The rookie passer and receiver Calvin Johnson (knee) each missed three days of practice after suffering injuries in Sunday's dramatic win over Cleveland.
Information from the Associated Press was used in this report