Muguruza was unable to overcome a left foot problem and retired hurt early in the second set of her second-round clash with American Varvara Lepchenko, losing 7-6 (9) 1-0 on Wednesday night on Pat Rafter Arena.
The 22-year-old Spaniard, one of several up-and-comers tipped to challenge the dominance of Serena Williams this year, was granted a medical timeout between sets and bravely attempted to play on but was unable to do so.
Muguruza said she started to feel the injury, in her heel, at 3-3 in the first set and initially suspected new orthotics might be the cause.
But the Venezuelan-born right-hander said the problem traced back to last season and the condition, known as plantar fasciitis, only flared up since returning to the court in pre-season.
“I’m not really worried because I felt it a lot, so it’s really necessary to do a lot of treatment and to keep it (from) getting worse,” she said.
“I will see now with my team and find out the problem and try to solve it as quick as possible. Hopefully it’s gone in couple of days.”
Lepchenko moves onto a quarterfinal match-up against Spanish sixth seed Carla Suarez Navarro, and impressed in the relatively short time she was on the court.
“I thought she was playing good. For sure she has been practising,” Muguruza said of Lepchenko.
“I think it’s always sometimes hard to play the first matches, but (she was) really solid and motivated to play.”