Ruben Ramirez Hidalgo posted a clear 6-4, 6-4 victory in ousting Simon on the opening day of the clay-court event.
Two other seeded players fared better in their first-round matches. No. 5 Marc Gicquel was a 6-4, 6-2 winner over Alessio Di Mauro and No. 6 Arnaud Clement took a 7-6 (7-1), 6-3 decision from Ernests Gulbis.
This week's top seed is Dominik Hrbaty, the 2004 runner-up at the Casablanca ATP stop.
This year's Grand Prix Hassan II winner will earn $75,000.