(CNN) -- Three-time champion Andy Roddick has equaled his earliest exit at the Legg Mason Tennis Classic as American title hopes evaporated in Washington.
The second seed was beaten by No. 13 Gilles Simon in his third-round tie on Thursday night as the Frenchman progressed into the quarterfinals with a surprisingly comfortable 6-3 6-3 victory.
With in-form Mardy Fish and John Isner also crashing out along with qualifier Ryan Sweeting, it is the first time since the hard-court tournament started in 1969 that no U.S. player has reached the last eight.
Roddick, last year's losing finalist, was knocked out in the third round in 2002 a year after winning the event for the first time.
"It was just a bad night, I don't have much of a defense for it and I don't think you can defend it," the world No. 9 told the ATP Tour website as he continues his preparations for next month's U.S. Open.
"I didn't feel right physically or mentally, it was just a pretty bad effort. I felt like I didn't do one thing right tonight and I honestly don't think it would have mattered who I played.
"I feel pretty lethargic and not quite as excitable as I normally am so it's something we might look into. I felt pretty rough physically in Atlanta and then last week I worked pretty hard, and here I just haven't been feeling quite right so I haven't been feeling well for some weeks."
Fish, who won the title in Atlanta, ended an 11-match winning streak as he bowed out 6-4 4-6 6-2 to fourth seed Marin Cilic.
The Croatian world No. 13 will next play in-form Serbian Janko Tipsarevic, who beat Colombia's Alejandro Falla 6-3 6-4 in a match that ended after 1 a.m. due to earlier delays caused by thunderstorms.
Atlanta finalist Isner lost to Belgium's Xavier Malisse on home soil for the second time this year, going down 6-4 3-6 7-6 (7-5).
Malisse will next play top seed Tomas Berdych, with the Wimbledon finalist making heavy weather of his match against 16th seed Andrey Golubev before beating the Kazakhstani 6-3 5-7 7-5.
Tipsarevic, who reached the semifinals last week in Los Angeles, had the previous day eliminated another in-form American, sixth seed Sam Querrey.
Simon's reward for reaching the quarterfinals for just the second time this year is a clash with comeback king David Nalbandian.
The Argentine, playing just his fifth event since hip surgery in May last year, thrashed unseeded Swiss Marco Chiudinelli 6-1 6-0.
World No. 10 Fernando Verdasco ended the hopes of Sweeting, winning 6-4 7-5 to set up a last-eight clash with eighth seed Marcos Baghdatis.
The Cypriot, a quarterfinalist in L.A. last week, battled past Ukrainian world No. 73 Illya Marchenko 6-3 6-7(5-7) 6-3.