Bryan is recovering in the U.S. after receiving a cortisone shot for an inflamed left shoulder that has bothered him since Wimbledon.
"I aggravated it pretty bad at the (U.S.) Open and only made things worse,'' Bryan said on the Davis Cup Web site. "I knew if I wanted a chance to play the rest of this year, I had to shut it down now. I can't even hit any balls.''
It will be the first time in 16 Davis Cup matches that Bryan and his twin brother, Mike, won't play together. The Bryans, who are 14-2 since debuting in 2003, helped the U.S. win the Davis Cup last year.
"He's been taking anti-inflammatories and getting a lot of treatment on it. I think it's fairly serious,'' Mike Bryan said Tuesday. "He obviously wanted to come here ... but it still wasn't good to go.''
Bryan's withdrawal is the second high-profile loss for the American team. Singles player James Blake, who has been a regular on the U.S. team since 2005, pulled out last week citing exhaustion, making way for the 39th-ranked Sam Querrey. Andy Roddick is the top U.S. player.
"The only thing that hasn't changed in the past week is that I need to win some singles match,'' Roddick said. "I'm probably the person least affected by the change - I've known for months now.''
Roddick, Blake and the Bryan brothers had featured in every American tie since 2005.
The 23rd-ranked Fish practiced on the clay Tuesday with Mike Bryan and could line up with him in the doubles.
"You don't need that much time to play with a partner and feel well,'' Mike Bryan said after the morning session.
Fish is 5-5 in Davis Cup play, including 4-4 in singles and 1-1 in doubles. His last appearance was in 2004, when he won one singles match and lost another as Spain beat the U.S. in the final in Seville.
The best-of-five series begins Friday with two singles matches, followed by the doubles on Saturday and reverse singles Sunday.
U.S. captain Patrick McEnroe doesn't see the reigning champions' task as impossible, despite the Spaniards playing on their favored clay surface and being led by No. 1-ranked Rafael Nadal.
"We are the underdog but we are not here strictly for our health. We are here because we think we can win,'' McEnroe said. "Obviously it's a difficult match but at same time it's a great opportunity for us to come out and play with great enthusiasm. No way do we look at this as a setback.''
Spain captain Emilio Sanchez Vicario said the home team won't alter its approach.
"When you have a pair like the Bryans that know each other well and consolidate each other, a match against them is always difficult,'' he said. "But Fish reached the quarters of Australian and U.S. Open and comes with talent even if he doesn't play doubles in a consistent fashion.''
The matches will be played on red clay at the Las Ventas bullfighting arena in front of 21,000 fans. A record 27,000 watched Spain beat the U.S. for the title in Seville.
"It's certainly not the traditional tennis venue but I think it will make for a great atmosphere,'' McEnroe said. "The courts are getting better. I'm sure by the time Friday comes around it'll be much better.''
Though Spain appears the overwhelming favorite now, Sanchez Vicario said the team was doing some adjusting of its own to the Spanish capital's high altitude.
"The altitude is something that influences the game very much, but we feel positive here and we will look to play the best we can,'' he said. "We came here early to accustom ourselves to it.''
Fish to replace injured Bob Bryan for U.S.
Van Der Vaart Wanted Barça
