The third round of the 2015 US Open Tennis Championships will kick off on Friday at Flushing Meadows in New York.

Rafael Nadal of Spain, who is looking to end his Grand Slam title drought, will face 32nd seed Fabio Fognini of Italy in the main match at the Arthur Ashe Stadium in New York.

The 14-time Grand Slam champion, who won the US Open in 2010 and 2013, kicked off his campaign with a four-setter win against Borna Ćorić in Day 1, which was followed by a straight-set victory against Diego Schwartzman.

On the other hand, Fognini is coming off a straight-set win against Pablo Cuevas on Wednesday, which came after he defeated Steve Johnson in the first round on Monday.

Nadal, who has not won a Grand Slam tournament since ruling the 2014 French Open, is considered the favorite heading into the match, but the Spanish tennis superstar remains wary of his opponent.

"He beat me twice this year," Nadal said of Fognini. "Before he didn't beat me. He played great in Beijing. Finally I won the match. He's a big, talented player. He's a tough opponent for everybody when he's playing well. So for everybody is a tough opponent, not only for me."

In other notable matches, top seed Novak Djokovic of Serbia will face 25th seed Andreas Seppi in the final match of the first session at Arthur Ashe Stadium. Defending champion and ninth seed Marin Čilić of Croatia will resume his title defense and will collide with unseeded Mikhail Kukushkin of Kazakhstan.

In the women's side, top seed Serena Williams of United States will face compatriot Bethanie Mattek-Sands.

Williams advanced to the third round following her straight-set victories against Vitalia Diatchenko of Russia and Kiki Bertens in the first two rounds.

Williams, who is looking to win her fourth Grand Slam title this year, is favored to win against Mattek-Sands. But the 33-year-old knows she has no room for complacency because she is aware her opponent will go all out on Friday.

"I know she's going to come out and I know what to expect," Williams said. "She's going to give 300%. She's a huge fighter. She has a great game, by the way. I know that will help me that I have to start out strong if I want to stay in the tournament. If not, I can go on vacation."

The complete 2015 US Open Day 5 schedule and match times are listed on the US Open website. Games will be shown live on ESPN and through online streaming via US Open Live and WatchESPN.