The school announced just before Friday night's season opener with Cal State Fullerton that Melton would be held out for eligibility reasons.
"As a precaution, De'Anthony Melton is being held out due to a potential issue regarding eligibility," the school said in a statement. "De'Anthony is a valued member of the USC community.
"USC is working diligently to independently investigate this matter in order to confirm that De'Anthony meets the NCAA eligibility requirements."
Melton was in street clothes during warmups.
He practiced throughout fall camp, but did not play during the Trojans' two closed scrimmages.
Melton's absence from the lineup comes after USC assistant Tony Bland was one of four assistant coaches accused of accepting bribes to steer players toward agents, financial advisors and apparel companies, as part of an FBI investigation. Bland was arrested in October and later appeared in New York with Auburn's Chuck Person, Adidas' Merl Code and custom clothier and former NBA referee Rashan Michel, in front of U.S. Magistrate Judge Katharine H. Parker.
Bland, who is on administrative leave, was indicted by a federal grand jury in New York earlier this week.
Bland is alleged to have taken at least $13,000 in bribe money. According to the Los Angeles Times, Bland allegedly helped facilitate payments of $5,000 and $4,000 to family members of two players. One player was identified as being on USC's current roster, while the other is a "rising freshman" or recruit.