An emotional Cobolli sat in tears after retiring from last week's second round in Vienna with a minor muscle strain, but the French Open runner-up still made the trip to Paris in the hope of recovering in time.
The withdrawal casts fresh doubt over Cobolli's prospects of making a maiden appearance at the ATP Finals in Turin.
The Italian is highly likely to secure the fifth berth and join Alexander Zverev, Carlos Alcaraz, Ben Shelton and Daniil Medvedev, but now faces a race to be fit for the event.
World number two Jannik Sinner will not take part due to a knee injury. Arthur Fils, Frances Tiafoe and Rafael Jodar remain in contention behind Cobolli, with Jodar currently occupying the final qualifying spot.
Jodar beat Alejandro Tabilo in straight sets in his opening match in Paris on Monday. He will face Casper Ruud in the next round.
Also still in the hunt are Alex De Minaur, as well as seven-time Paris champion Novak Djokovic and Taylor Fritz, both of whom need a deep run this week to keep their Turin hopes alive.
