The world number one revealed his late decision to skip the event he won a year ago during a sweep of the last three events of the 2011 season.
Federer, 31, said he felt he needed to let a few niggles heal to be fully fit for the start of the World Tour Finals in London a week from Monday.
The upset victory by Argentine Del Potro denied Federer a sixth title from the last seven editions at the St Jakobshalle and kept him from the 77th of his career.
"I'm not going to Paris, it's too much for me," Federer said.
"I've already told (tournament director) Guy Forget. I have some niggling stuff that I want to heal, I don't want to take a chance for London.
"Missing Paris is disappointing. I remember how great it was to win the title a year ago. I had one of the best weeks of my life there in 2011."
With old rival Rafael Nadal also missing after ending his campaign early due to the knee injury which has kept him off court since June, the Paris field will now be led by second seed Novak Djokovic and US Open winner Andy Murray.
Djokovic beat Murray for the Shanghai title this month, with neither man playing since.
Murray withdrew from the Swiss Indoors in Basel, claiming a back niggle, to the dismay of organizers faced with his second pullout in as many years.
Federer's place in the draw for the Paris Masters has been taken by Romanian lucky loser Victor Hanescu.
With all 16 seeds getting first-round byes, lesser contenders will begin play, with French players Benoit Paire, Paul-Henri Mathieu -- both defeated by Federer in Basel -- and Michael Llodra receiving wildcards.
Spain's David Ferrer, who clinched a third Valencia Open on Sunday, takes the third seeding ahead of Tomas Berdych.
Also in the field is fellow World Tour Finals qualifier del Potro.
Two places in the London field remain up for grabs with France's Jo-Wilfried Tsonga, Serb Janko Tipsarevic, Spaniard Nicolas Almagro and France's Richard Gasquet all in contention.