Fifth seed Federico Delbonis was bundled out of the Cordoba Open after a shock straight-sets defeat to Carlos Taberner on Tuesday.
The 31-year-old Argentine, who is currently ranked 41st in the world, went down 6-4 6-2 to the 111th-ranked Spaniard.
Former top 10 player Fernando Verdasco was also beaten on Tuesday, going down to Argentine Sebastian Baez 7-6 (8-6) 7-5.
The 38-year-old Spaniard dropped out of the top 100 last year for the first time since 2004 after a difficult season with a long-term leg injury and COVID-19 prior to the French Open.
Baez will play Chilean third seed Cristian Garin in the second round, while Taberner will meet qualifier Alejandro Tabilo after he beat wild card Francisco Cerundolo 6-4 6-1.
Lucky loser Colombian Daniel Galan also progressed into the last 32 after a 7-5 6-3 victory over Bolivian Hugo Dellien, while sixth seed Albert Ramos-Vinolas triumphed 6-4 6-3 over Andrej Martin.