Barcelona - Novak Djokovic suffered a surprise defeat in his latest comeback from injury at the Barcelona Open on Wednesday as Rafael Nadal got his bid for an 11th title safely off the ground.
Djokovic had been on course to meet Nadal in the quarter-finals but a disjointed display gave his second round opponent Martin Klizan, ranked 140th in the world, a 6-2, 1-6, 6-3 victory.
World number one Nadal endured no such problems against compatriot Roberto Carballes Baena, winning 6-4, 6-4.
While Klizan goes through to meet Spain's Feliciano Lopez in the last 16, Djokovic will now have to reset, with the French Open next month fast approaching.
His latest setback is not the shock it once might have been.
After losing in the Australian Open fourth round in January, Djokovic underwent surgery to correct an injury to his right elbow, which had been troubling him for almost two years.
The problem has coincided with a prolonged slump in form for the 12-time major champion, who has reached only one Grand Slam final since winning the French Open in 2016.
But a reunion with long-time coach Marian Vajda this month had sparked hopes Djokovic could yet steer his career back on track.
There were encouraging signs in Monte Carlo last week, despite a three-set defeat to Dominic Thiem, with the Serb declaring there he was finally playing without pain.
He was well below his best against Klizan, however, as the Slovak claimed his first victory against a top-20 opponent in just over two years.
After a miserable opening set, Djokovic looked to have found his groove in the second as he dominated from the baseline and began to find the corners with his forehand.
But, while at his best Djokovic was always ice cool under pressure, he buckled in the decider, planting a Klizan lob into the net before a nervy forehand volley conceded the crucial break at 4-3.
Serving for the match, Klizan double-faulted but he had three chances to close out and clinched the second when another Djokovic forehand missed its mark.
Nadal is going for his 11th Barcelona title this week and the top seed looked ominously comfortable against Carballes Baena.
The 31-year-old will now face another Spaniard in Guillermo Garcia Lopez, who progressed after Kei Nishikori retired.
Nishikori had lost to Nadal in the Monte Carlo Masters final on Sunday and he pulled out after conceding the first set to Garcia-Lopez 6-3.
Fatigue, and pain in his troublesome right wrist, appeared to prompt the withdrawal from Japans world number 22, who told reporters after the match: "I started feeling discomfort again during the first set and I did not want to take any risks."
It completes a double setback for Asian players as Chung Hyeon, the South Korean who was a surprise semi-finalist at this year's Australian Open, withdrew before play in Barcelona even began.
Barcelona Open results on Wednesday (x denotes seeding):
Guillermo Garcia-Lopez (ESP) bt Kei Nishikori (JPN x14) 6-3 - retired
Martin Klizan (SVK) bt Novak Djokovic (SRB x6) 6-2, 1-6, 6-3
Stefanos Tsitsipas (GRE) bt Diego Schwartzman (ARG x7) 6-2, 6-1
Jozef Kovalik (SVK) bt Guido Pella (ARG) 6-3, 6-3
Dominic Thiem (AUT x3) bt Jaume Munar (ESP) 7-6 (10/8), 6-1
Grigor Dimitrov (BUL x2) bt Gilles Simon (FRA) 6-2, 6-1
Karen Khachanov (RUS x16) bt Leonardo Mayer (ARG) 6-4, 6-3
Rafael Nadal (ESP x1) bt Roberto Carballes Baena (ESP) 6-4, 6-4
Albert Ramos Vinolas (ESP x10) bt Rogerio Dutra Silva (BRA) 3-6, 6-3, 6-4
Pablo Carreno-Busta (ESP x5) bt Benoit Paire (FRA) 6-3, 6-3
Pablo Andujar (ESP) bt Bjorn Fratangelo (USA) 6-4, 6-3