The knee problem meant Nadal had to pull out of last month's Paris Masters
World number one Rafael Nadal has ruled himself out of Spain's Davis Cup final against Argentina on 21-23 November.
The 22-year-old, who pulled out of the end-of-year Masters Cup in Shanghai, has been struggling with tendonitis in his right knee.
"After a long and very positive season, it pains me to miss the two main objectives of the year, Shanghai and the Davis Cup final," he said.
"It's a difficult time, I did everything to try and make this final."
Nadal, who won both Wimbledon and the French Open this year, last played at the Paris Masters in October, when he was forced to pull out because of his injury problems.
He says they are a result of the over-intensity of the ATP calendar.
"I am used to playing with pain but this was a new and different pain I cannot control," he said on his website on Monday.
Spain team doctor Angel Ruiz-Cotorro said Nadal would need three to six weeks to recover and although the injury is not career threatening, playing against Argentina in the Davis Cup later this month was not worth the risk.
"Rafa comes in off a very tough year and his body has been warning him for weeks," Ruiz-Cotorro said. "It's an acute injury that needs time to recuperate.
"If he played in Argentina, it could become worse."
Nadal won both his singles matches when Spain beat defending champions the USA 4-1 in Madrid in October to reach the final, so his absence will be a big blow to their chances of winning the tournament for the third time since 2000.
Team captain Emilio Sanchez Vicario called up world number 56 Marcel Granollers to replace Nadal on Tuesday.
He also selected David Ferrer, Feliciano Lopez and Fernando Verdasco, with Santiago Ventura, ranked 122nd, travelling as the first substitute.
Argentina will be represented by Juan Martin del Potro, David Nalbandian, Jose Acasuso and Agustin Calleri for the best-of-five series on an indoor hard court in Mar del Plata.