Roddick, a three-time champion of this US Open Series event, came out flat against the 13th-seeded Frenchman in a match that started just before 11 p.m. because of a 4 1/2 -hour weather delay.
Roddick, ranked ninth in the world, was the third highly seeded American to lose over the past two days.
Unseeded Xavier Malisse of Belgium beat fifth-seeded John Isner 6-4, 3-6, 7-6 (5) on Thursday. Sixth-seeded Sam Querrey lost in straight sets to Serbia’s Janko Tipsarevic on Wednesday.
“It was just a bad night,” Roddick said. “I don’t really have any defense for it. I didn’t feel right physically. I didn’t feel right mentally. I wish I had answers for you right now, but I just don’t.
“(But) I promise you, I’m going to figure this out before I do that again.”
Roddick, who was 26-4 through April, has lost five of his last 14 matches on tour. He had won his previous two matches against Simon in straight sets.
“The difference is that I was able to return his serve today,” Simon joked about the match that ended just before 1 a.m. “He wasn’t able to hit winners versus me because the court was a little slow and I was moving well.”
In other matches Thursday, top-seeded Tomas Berdych of the Czech Republic beat 16th-seeded Andrey Golubev of Kazakhstan, 6-3, 5-7, 7-5; and third-seeded Fernando Verdasco of Spain defeated American Ryan Sweeting 6-4, 7-5.
Malisse overcame 18 aces by Isner and took advantage of a number of mistakes by his 6-foot-9 opponent, who had won each of his seven previous tiebreaks at this event.
“He serves well, and because of that you have a little more pressure on your serve,” Malisse said of Isner, who leads the ATP tour in aces. “I just tried to get the serve back. That’s his big weapon. You take what you can get, and right now I’m just happy to be in another quarterfinal.”
The weather delay might have affected the players.
“I don’t know, maybe,” Verdasco said. “Of course waiting is not an easy thing.”
The three doubles matches scheduled for Thursday were pushed to Friday.
In Carlsbad, California, American teenager Coco Vandeweghe upset Wimbledon finalist Vera Zvonareva of Russia 2-6, 7-5, 6-4 in the second round of the Mercury Insurance Open on Thursday.
Vandeweghe, ranked No. 205, rebounded from a terrible start to surprise Zvonareva, the world’s No. 9 ranked player.
The 18-year-old Vandeweghe outplayed Zvonareva in both the second and third sets for the biggest win of her short career.
“It’s awesome to beat someone at that high of a level,” Vandeweghe said. “She’s been doing so well. I’m just excited that I was able to play at a high level to beat her.”
Vandeweghe, who won three qualifying matches to get into the main draw, won her second straight match after dropping 13 of her previous 15 career WTA matches.
The third-seeded Zvonareva appeared to be poised for an easy win when she broke Vandeweghe’s serve the first three times in the opening set. By the time Vandeweghe held serve, she trailed 5-2.
“The first set I was pretty nervous to say the least,” Vandeweghe said. “I wasn’t playing the way I had been playing to get there.”
But she teenager seemed to settle down as she received loud backing from the crowd. After the two traded early service breaks in the second set, Vandeweghe used a late break before serving out to even the match.
Vandeweghe served for the match at 5-3, but Zvonareva converted on her third break point to cut the lead to 5-4. But Vandeweghe hit a crushing forehand winner in the next game to secure the upset on her first match point.
“I don’t think she surprised me. I’ve seen her play before,” said an emotional Zvonareva, who cried while speaking with reporters. “It’s more that I surprised myself. I started pretty good and then I just started playing stupid. I didn’t change anything, I just kept playing stupid.”
Vandeweghe moved into the quarterfinals against Svetlana Kuznetsova of Russia, who topped Italy’s Sara Errani 6-1, 5-7 (5), 7-5.
Fifth-seeded Flavia Pennetta of Italy advanced to the quarterfinals with a 6-4, 7-6 (5) win over Russia’s Maria Kirilenko.
Pennetta made two early breaks stand up to win the first set before she fell behind 5-2 in the second. She then reeled off four straight games to take a 6-5 lead.
Pennetta dropped her serve at love to force the tiebreaker. Neither player had led by more than two points in the tiebreaker when Kirilenko saved one match point at 6-4 before Pennetta closed out the second-round match.
“After the first set, I just relaxed a little bit,” Pennetta said. “She was making some mistakes at the end of the first set so I was thinking she was going to do the same. But she started to play better and more aggressive. I was a little too far from the (base)line and I was running too much.”
Pennetta, who has beaten Kirilenko in their past three meetings, will face No. 2 seed Samantha Stosur of Australia in the next round.
“I have to rest now and be ready for running so much,” Pennetta said. “When she hits the ball it’s really powerful. My return is going to be really important.”
In another second-round match, Slovakia’s Daniela Hantuchova defeated Zheng Jie of China 6-2, 6-1.
