A few hours later the tournament was rocked again when seventh seeded Czech Tomas Berdych announced he was withdrawing due to gastroenteritis, handing Nadal a free pass.
Thousands of tennis fans had arrived at the Crandon Park complex expecting a day of pulsating action but instead were left with two women's doubles matches.
When it was announced prior to the start of the night session that the Nadal/Berdych match would not be played the stadium erupted in an angry chorus of boos, many showing their disgust by turning and heading for the exits.
"Sorry for Kei. Sorry for Tomas. Sorry for the tournament. Especially sorry for the fans," said Nadal about the double walkover. "It's very unlucky, very unusual for something that can happen.
"I cannot remember that (ever happening)."
That would be because a double walkover in the semi-finals of an ATP Tour event is unprecedented in the professional era.
The walkovers, however, left the Miami Masters with a mouth-watering final featuring the world's top two players, Nadal and Djokovic set to clash for the 40th time.
Nadal leads the head-to-head 22-17 but has never lifted the Miami title despite reaching the final three times.
"Only chance to win against Novak is play to the limit, play my best and hope that he is not going to have his best day," said Nadal. "For me, I am going on court and trying my best. (It) doesn't make any difference if it's one tournament or another one.
"For sure, Miami is a very important tournament that I never had the chance to win in the past.
"It is my fourth final. It's positive results. To be able to play four finals in one tournament is because you did well, and I am going to try to be ready for Sunday."
Berdych said that all seemed normal following his quarter-final win over Ukraine's Alexandr Dolgopolov until he woke up Friday morning.
"I just woke up with a pain in my stomach, just went for toilet and got really strong diarrhea," said Berdych. "Since then, it starts to go on and on. More time, diarrhea and then also throwing up and stuff like that.
"I lost so much of the liquid and all the possible energy I could have.
"Came here. Tried to do as much as I could, see the doctors, receiving the IV and basically not with good results."
Nishikori had reached the last four after registering a pair of three-set upsets, defeating Spanish fourth seed David Ferrer in fourth round followed by a quarter-final win over Swiss 17-times grand slam winner Roger Federer.
The Japan number one said that the groin had been bothering him for some time but it flared up against Federer in a match that ran late into an unusually cool evening in south Florida.
Nishikori also retired during the Delray Beach tournament in February for a similar complaint.
"I really felt the last match against Roger, the quarter-final," he said. "It's really sad, of course, semi-final in a big tournament.
"Was really playing well and beating (Grigor) Dimitrov, David (Ferrer) and Roger (Federer). I was really excited to play here.
"But unfortunately I couldn't move side-to-side. Just tried to warm up today, but I couldn't move."
The walkover was the second of the tournament for Djokovic, who had a free pass in the third round when Florian Mayer pulled out with a groin injury.
Djokovic should be well rested for Sunday's final, not having played in four days and contested just three matches the entire tournament.
"It's such a big event, and from a player's perspective, it's never nice to have a walkover to go on to the finals without a fight," said Djokovic. "Now the only thing I can think about is finals and focus on winning the title."
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