The match was originally scheduled for Thursday but was postponed because of rain. If the weather holds up, Nadal will play Albert Ramos later Friday. Ramos defeated Kei Nishikori of Japan 6-4, 7-6 (4).
Playing two matches in the same day should be a good test of Nadal's balky left knee. He took seven months off and returned in February after a nagging case of tendinitis.
Nadal reached five straight finals heading into Barcelona, but lost to Novak Djokovic last weekend. That ended his eight-year winning run at Monte Carlo and raised questions of whether he's ready to compete next month for the much more grueling French Open title.
"We'll see how the day goes. For the moment, I've done the important thing, which is to win the first match," Nadal said. "I'm taking it step-by-step. Let's see if I can play better in the second match."
Also, Tommy Robredo rallied from a set down to eliminate sixth-ranked Tomas Berdych 3-6, 7-6 (5), 6-3. The unseeded Robredo hit a winner that clipped the baseline to break Berdych's serve for the fourth time on match point.
Robredo will face Milos Raonic later Friday in the quarterfinals. The Canadian defeated Ernests Gulbis 6-2, 7-6 (6).
Philipp Kohlschreiber of Germany defeated Martin Klizan of Slovakia 1-6, 7-6 (2), 7-6 (5). Kohlschreiber advanced to the semifinals after Thomaz Bellucci withdrew before their quarterfinal.
Nadal had a sluggish start and Paire hit a winner off one of his second serves to get the early advantage.
After squandering three break points in Paire's first service game, Nadal broke back to pull even at 3-3 with defensive slices that Paire eventually sent long.
Nadal's steady ground game forced Paire to make three errors in the tiebreaker.
He took control of the second set when he broke Paire at love to go ahead 3-2 after the Frenchman's serve failed him and he hit consecutive double-faults.
Paire had a chance to break back in the next game, but he hit long and slammed his racket into the ground. Nadal went on to take the game and sealed the match when Paire's drop shot fell well short.
Nadal last lost at the Barcelona Open 10 years ago to Spain's Davis Cup captain, Alex Corretja.