Bernard Tomic blew a one-set lead and a second set break of serve against Uruguayan Pablo Cuevas as he crashed out of the Valencia Open 3-6 6-3 6-4 on Wednesday.
The third-seeded Australian led 2-0 in the second set before the world No.33 fought back and just one break of serve was enough in the decider to set up a quarter-final meeting with Portugal’s Joao Sousa or Frenchman Benoit Paire.
Britain’s Aljaz Bedene is also out after losing 6-3 6-4 to Canadian Vasek Pospisil.
American Steve Johnson will face second seed Feliciano Lopez in the second round after defeating Slovakia’s Martin Klizan 6-3 6-4.
Top seed and three-time champion David Ferrer isn’t in action until Thursday when he faces German qualifier Daniel Brands.