Australian second seed Bernard Tomic crashed out of the Abierto Mexicano Los Cabos in the second round as Feliciano Lopez won through to the quarter-finals.
Tomic suffered a shock 7-6 (7-4) 3-6 6-4 loss to Serbia's Dusan Lajovic at the ATP 250 event on Wednesday.
Despite posting 10 aces and converting two break points, Tomic came unstuck against Lajovic, after winning just 12 of 65 first return points in the one hour, 51-minute contest.
It does not get any easier for Lajovic, who will meet seventh seed Nicolas Almagro in the last eight.
Almagro got the better of fellow Spaniard Guillermo Garcia-Lopez 7-6 (7-4) 6-3.
Another seed fell in the form of Sam Querrey - the fourth-seeded American - who went down 7-6 (7-1) 6-3 to Santiago Giraldo.
Giraldo and Pablo Carreno Busta will go head-to-head in to the next round following the latter's 6-0 6-3 triumph against Austin Krajicek.
Top seed Lopez booked his spot in the quarters thanks to a straight-sets win over emerging American teenager Reilly Opelka.
Lopez saved all four break points faced as he dispatched Opelka 6-3 7-6 (7-3) to earn a matchup against Julien Benneteau, who overcame Horacio Zeballos 6-1 6-7 (1-7) 6-1.
Big-serving Croatian and third seed Karlovic won his second-round match, outlasting qualifier Mischa Zverev.
Karlovic was too good for the German 6-3 3-6 6-3 after almost one and a half hours on court.
In a trademark serving display, Karlovic fired down 18 aces, winning 80 per cent of his first serves.
Next up for Karlovic is Marcel Granollers, who accounted for Tobias Kamke 7-6 (7-2) 6-2.