Valencia - Australian number three seed Bernard Tomic blew a one set lead against Uruguayan Pablo Cuevas as he exited the Valencia Open 3-6, 6-3, 6-4 on Wednesday.
Tomic was even a break up early in the second set before the world number 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.