The Argentine forward has been recuperating from a knee ligament damage sustained in a La Liga contest against Las Palmas on September 26.
Speculations are rife that the 28-year-old would return to the field for the Catalans in the game against arch-rivals Real.
“The risk of aggravating the injury if Messi plays the Clasico is high,” Homero was quoted as saying by goal.com on Wednesday.
The doctor also doubts whether the ace striker can recover full fitness before the clash.
“I don’t think that he can get in condition to play the Clasico,” he said.
“The coach (Luis Enrique) cannot rely on a newly recovered player.”
Messi has been left out of the Argentina squad for upcoming World Cup qualifiers against Brazil and Colombia because of the injury.