The world number one struggled to find any kind of form and lost 6-4, 6-4 to veteran Spaniard Francisco Clavet after throwing up for most of the previous night.
"I got sick last night about five minutes after ordering room service and was sick as a dog after that," Hewitt said.
"I got to bed late. I could feel it as soon as I started running tonight and it just got worse.
"I had a drink, which got me through a couple of games, but I was fighting a losing battle after that.
"I didn't feel great and I didn't play well out there. I just felt that I couldn't rally and I had to go for shots when most of the time it wasn't really on. But I still had a lot of chances to win, even though I played so bad.
"Clavet played as well as he could, he mixed the ball up well, but I still feel it was more because I couldn't go out there and play my game I wanted to play."
Clavet, a 34-year-old left-hander ranked 178th in the world, became the fourth-lowest ranked player to beat a world number one since 1973.
UNFORCED ERRORS
He took advantage of Hewitt's 33 unforced errors in a match lasting just over an hour and a half and changed the pace cleverly on several occasions in the second set when Hewitt dropped his service three times.
Hewitt saved one match point on Clavet's serve before hitting into the net again on the second.
Clavet's big weapon was his forehand and he foiled Hewitt regularly through the second set with fierce passing shots close to the tramlines.
"Hewitt is the best defensive player in the world. He's unbelievable, very fast. As fast as you play against him, he returns and defends," Clavet said.
"I had to mix up my game to play some slice, some top-spin, slow balls, suddenly accelerate.
"When you get close to the victory against the number one player, you get a little bit tight. I think I kept the pressure on well, especially at the end and I think that's the key to my victory."
Clavet, who says this probably his last season on the men's professional tour, moves on to a meeting in the last 32 against Lee Hyung-taik of South Korea.
Lee advanced with a 6-7, 6-2, 6-1 win over 25th seed Xavier Malisse of Belgium.
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