With the Australian Open looming, top seed Muguruza bowed out of the lead-up tournament when she was ahead 2-1 in the third set of the second-round clash on Tuesday as in-form Serb Aleksandra Krunic progressed 5-7 7-6 (7-3) 1-2 to the quarter-finals.
A quarter-finalist at the slam in Melbourne last year, Spanish star Muguruza is now out of contention to claim the number one WTA ranking, which Simona Halep can cement with victory at the Shenzhen Open on Wednesday.
"I felt in trouble in the second set when I was 2-0 up," Muguruza, 24, said afterwards.
"I start to feel my calves were cramping. I continued to think that with the match they might go away, but then they were increasing, increasing. And then I had a lot of part of my body cramping.
"I cannot believe it. I don't know. It's a shame because I always come here excited the first tournament, and this one was bad luck, I guess."
The Australian Open gets underway on January 15 and Muguruza is expected to challenge for silverware, having claimed Wimbledon in 2017.