Switzerland's Roger Federer reacts after winning his match against Spain's Fernando Verdasco in the third round of play at the 2012 US Open tennis tournament, Saturday, Sept. 1, 2012. (Photo: AP)
Five-time champion Federer will face either Czech sixth seed Tomad Berdych or Spanish 11th seed Nicolas Almagro for a place in the semi-finals.
It will be the top seed's 38th Grand Slam quarter-final.
"Mardy Fish has withdrawn for health reasons," said the spokesman.
Fish, 30, missed two months of the season earlier this year because of a heart problem.
He was hospitalised after the Miami Masters in March when his heart rate increased to three times its normal resting rate.
The American then underwent a procedure called a cardiac catheter ablation in Los Angeles on May 23 to correct faulty wiring in his heart.
(For more sports news and updates, follow Ahram Online Sports on Twitter at @AO Sports and on Facebook at AhramOnlineSports)
Short link: