The Indians fought hard before going down 6(4)-7, 4-6, 6-3, 3-6 to Denis Istomin and Farrukh Dustov in a must-win encounter at the Sport Complex Pahlavon.
The Indian team was banking heavily on Paes and Bopanna to pull one back in order to keep Sunday's reverse singles matches consequential, after rookies Sanam Singh and Yuki Bhambri lost their respective singles matches on Friday.
But Istomin and Dustov caused a major upset when they handed defeat to Paes and Bopanna, both of whom are ranked in the doubles top-10.
While the first set was stretched to the tie-breaker with none of the teams ready to bow down to each other, the Uzbeks did well to snatch the second.
The Indians though bounced back in the third set to keep their chances alive. However, they completely ran out of steam in the fourth to surrender meekly.
Yesterday youngsters - Sanam Singh and Yuki Bhambri - lost their singles matches in straight sets against Istomin and Dustov, respectively in what turned out to be lop-sided contests.
Sunday's reverse singles will be dead rubber. Bhambri would take on Istomin in the fourth singles. The only time they had met before was in Miami 2010 and Istomin emerged victorious. Asian Games gold medallist Sanam will take on Dustov in the other match.
Earlier, top doubles player Mahesh Bhupathi opted out of India's Davis Cup tie against Uzbekistan to allow tour partner Bopanna pair with Paes.
AITA (All India Tennis Association) had said that since Davis Cup captain SP Misra wanted two singles players, the selection committee was to choose two doubles specialists from among Paes, Bhupathi and Bopanna.