American Steve Johnson ousted world No.16 Feliciano Lopez 6-4 7-6 (7-3) to reach the quarter-finals as the seeds continued to fall at the Valencia Open on Thursday.
The top five seeds all failed to make the last eight as Germany’s Mischa Zverev shocked Fabio Fognini 6-2 7-6 (7-3) and Joao Sousa beat France’s Benoit Paire 6-3 2-6 6-3.
Top seed and three-time champion David Ferrer withdrew from the tournament on Wednesday due to an elbow injury.
Spain’s Guillermo Garcia-Lopez, at six, is the highest remaining seed in the draw and will face Johnson in Friday’s quarter-finals after sweeping aside Japan’s Taro Daniel 6-3 6-4.
Seventh seed Roberto Bautisita Agut eased past Russian newcomer Andrey Rublev 6-2 6-3 and will take on Zverev in the last eight.
Portugal’s Sousa will meet third seed Bernard Tomic’s conqueror, Uruguayan Pablo Cuevas.
German qualifier Daniel Brands faces Canada’s Vasek Pospisil after overcoming lucky loser Albert Montanes, who had replaced Ferrer, 6-2 6-2.