Fish, 31, has been working his way back into competitive tennis since a heart condition was discovered in March 2012. He withdrew from a match in North Carolina Tuesday because of heat stroke.
He has played only eight matches this year, going 3-5, and, by missing the U.S. Open, won't have played in any Grand Slam events in 2013.
"Friends, unfortunately my health won't allow me to compete this year at the U.S. Open. Thank you for all your support," Fish said on his Twitter feed.
In March 2012 Fish's heart was racing uncontrollably after a match. Two months later he underwent a procedure to correct electrical connections in his heart. He's appeared in only 10 tournaments since then.
Fish has won six ATP tournaments in his career. He played in three finals in 2011 when he ranking reached No. 7 in the world. With health issues limiting his playing time, Fish had currently ranked 173rd.