Melo is being held out due to an unresolved academic issue from the first semester, according to a source.
The Orange play the Fighting Irish at 6 p.m. ET Saturday.
Melo played against Pitt Monday, before the second semester began. Melo set a career-high with 10 rebounds. He also had 10 points.
According to the source, the school is hoping the matter can be cleared up next week. The Orange host West Virginia Jan. 28.
The university did not give further details, citing school policy and federal student privacy laws.
Andy Katz is a senior college basketball writer for ESPN.com.