Seeded third, Bopanna and his Canadian partner Daniel Nestor were shocked by Spanish duo of Rafael Nadal and Pablo Carreno Busta in straight sets with the scoreline reading 6-7(3) 4-6.
There was more heartbreak stored for India later in the day when veteran Paes and Germany's Andre Begemann were shown the door by American-Australian duo of Jack Sock and Bernard Tomic.
The wildcard holder pair of Paes and Begemann fought hard before going down 6-3 5-7 7-10 in super tie-breaker of the match in the USD 4,164,780 ATP 500 event.