By contrast, top-seeded Andy Murray opened his bid to recapture the title he lost last year to Grigor Dimitrov with a comfortable 6-4, 7-5 win over Taiwanese qualifier Lu Yen-Hsun, and French Open winner Stan Wawrinka began his bid for a first grass court title by defeating Australian Nick Kyrgios 6-3, 6-4.
Watched by Chelsea soccer manager Jose Mourinho and the former king of Spain, Juan Carlos, Nadal was kept under pressure throughout the match by the free-hitting Ukrainian, who ended a three-match losing streak with his second successive victory over his Spanish opponent.
Dolgopolov held three points for a 4-0 first set lead as Nadal struggled to make an impression, and although the fifth-seeded Spaniard eventually worked his way into the match he faced a match point in the tiebreaker before taking the second set.
In the final set, Nadal broke for a 2-1 lead, but Dolgopolov levelled at 4-4. Nadal then held three break points in the next game, but it was Dolgopolov who broke at 5-4 to claim victory with his second match point.
"I was fighting in every point," Nadal said. "I was with the right concentration, with the right motivation, don't giving up when I had tough moments.
"I not happy I lost a match that I had a chance to win, but that's it. The good thing is I am positive mentally. I feel myself playing well. I hope to have some more good days of practice here and some good rest at home, and I gonna come back strong with a good week of practice before Wimbledon."
Despite his defeat, the Spaniard believes that with his victory in Stuttgart he has played enough matches as he heads into Wimbledon in a little under two weeks.
"I played five matches the year that I won here in 2008, and this year I already had five matches," he said. "This week I lost an opportunity, but my feeling, my thoughts are no different today than yesterday. I am playing better than before, and enjoying more on court than before."
Wawrinka, playing his first match since defeating Novak Djokovic to lift the French Open trophy and wearing check shorts similar to those which drew so much attention in Paris, needed patience before eventually gaining an advantage over Kyrgios.
A backhand error from his opponent gave the Swiss a break and a 5-3 lead, and after serving out the set to love Wawrinka, he swiftly confirmed his lead by breaking for 2-1 in the second set.
The No. 2 seed then had to fight off three break points at 3-2 before securing victory with his ninth ace.
"It was good, really good start," Wawrinka said. "I'm feeling quite good, for sure. Still need more time on the grass, more adjustment especially for moving. Sometimes I'm not moving that well, but today it was a great match."
Dimitrov completed a 4-6, 6-3, 6-4 victory over American 2010 tournament winner Sam Querrey after their match had been suspended overnight at one set all.