Williams won both her singles matches and tried to lift the United States into the Fed Cup final against Italy by returning to the court with doubles specialist Lisa Raymond, but the American duo fell 7-5 7-6 to Nadia Petrova and Elena Vesnina.
"I'm really disappointed because I tried really hard and I really wanted to win," the 27-year-old Williams told reporters.
"That's why I was here. It's good to know that I gave a hundred percent, but it's bad to know it wasn't enough this time."
U.S. captain Zina Garrison praised Williams and the entire squad for the way they battled.
"I'm extremely proud," Garrison said.
"First let's talk about Venus. I mean, coming off of Wimbledon, coming here, stuck in the airport for hours and hours and hours. Then getting here, very excited to be here, wanted to do whatever it took, wins two matches, then having to play the doubles.
"They (Williams and Raymond) just came up a little short. It really shows the heart of both of them and the rest of the team, as well."
The 33-year-old Raymond, ranked number two in the world in doubles with a 10-3 Fed Cup doubles record, was crushed by the defeat.
"I'm extremely, extremely disappointed obviously for a million different reasons," said Raymond, winner of 65 career doubles titles.
"This is what I play for. I wish I would have been able to come up with the goods today, not only for everybody but for the U.S. Just wasn't able to do it."
The Americans were playing without Venus's sister Serena, who pulled out due to injury.
Vania King, who played the opening singles, and Meilen Tu, who played the second singles on Sunday, were both routed by their Russian opponents.
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