The UFC is in jeopardy of losing its UFC 222 main event on March 3 in Las Vegas.
The UFC has not officially pulled Holloway from the event but is expected to do so shortly. The promotion is already in the process of exploring other options for its main event.
This will mark the second time a title fight between Holloway and Edgar has fallen through. The two were supposed to meet at UFC 218, on Dec. 2 in Detroit, but Edgar was forced out with an injury.
Fighting out of Waianae, Hawaii, Holloway (19-3) is riding a 12-fight win streak. ESPN ranks Holloway the No. 5 pound-for-pound fighter in the world.
Edgar (22-5) has not fought since May 2017.
UFC 222 takes place at T-Mobile Arena.