The comics legend will not be able to attend his scheduled public events "for the near future", a Wizard World representative said.
Lee will not appear at Ohio Comic Con next weekend.
He has also cancelled his appearance at Toledo-Lucas County Public Library's Authors! Authors! event on September 27, reports Toledo Blade.
His agent only said that the 89-year-old had to cancel the event for the second time due to "a very serious circumstance".
Lee pulled his appearance at the Hero Complex Film Festival in May, claiming fatigue.
In the past month, he has attended Dragon Con, Baltimore Comic-Con and Comikaze Expo.
He is scheduled for Wizard World New Orleans and various other events in the coming months.