Top-ranked Novak Djokovic of Serbia and Victoria Azarenka of Belarus will try to defend their titles at the $9.6 million ATP and WTA Miami hardcourt event that begins on Tuesday.
The showdown stretches for nearly a fortnight and comes after Djokovic was upset in the Indian Wells semi-finals and Azarenka beat World No. 2 Maria Sharapova in Sunday's final, as she did in last year's Miami final.
Djokovic was upset by big-serving American John Isner, who lost to World No. 3 Roger Federer in the Indian Wells final.
Now thanks to the first-round byes for Miami's high seeds, Djokovic is off until Saturday when he faces either Argentina's Leonardo Mayer or Cypriot Marcos Baghdatis.
"It's still a week to my first match, so I'm going to take some time, regroup," Djokovic said. "I feel physically well. I think I'm playing equally well. I'm confident ahead of the Miami tournament."
Djokovic defeated World No. 2 Rafael Nadal in last year's final, adding that title to his 2007 Miami crown.
The five-time Grand Slam champion comes into the event off a Grand Slam title at the Australian Open, just as he did last year.
Djokovic, who has captured the past three Grand Slam titles, could join Pete Sampras and Andre Agassi as the only three-time men's champions at Miami and become the first man since Federer in 2005 and 2006 to win back-to-back titles.
Nadal, a 10-time Grand Slam champion, has never won the Miami crown despite three trips to the finals, settling for runner-up honors in 2005 and 2008 as well as last year.
Nadal will open against either fell Spaniard Pablo Andujar or Colombia's Santiago Giraldo.
Federer, who has won a record 16 Grand Slam crowns, has not won the Miami crown since 2006 but is on a roll, having won three tournaments in a row with titles at Rotterdam and Dubai as well as Indian Wells.
World No. 4 Andy Murray of Britain, who crashed out in the second round at Indian Wells, will try to bounce back at Miami, where he defeated Djokovic in the 2009 final.
Murray will open against either Uzbekistan's Denis Istomin or Colombia's Alejandro Falla while Federer's first foe will be either US wildcard Ryan Harrison or Italy's Potito Starace.
Isner, ranked 10th, will open against either US countryman James Blake or Russia's Nikolay Davydenko.
On the women's side, Azarenka's first match will be against either a qualifier or Dutchwoman Michaella Krajicek while Sharapova, on the opposite end of the draw, starts in round two against a qualifier or Israel's Shahar Peer.
Czech third seed Petra Kvitova had the worst luck of the draw, with a bye into round two against either Japan's Kimiko Date-Krumm or US wildcard Venus Williams, a three-time Miami champion with seven Grand Slam singles titles.
Williams, like her sister Serena, is coming back after a long injury absence.
Chinese eighth seed Li Na, the reigning French Open champion, opens against a qualifier or Italy's Alberta Brianti. She could face compatriot Peng Shuai in the round-of-16 and Sharapova in the quarter-finals.
Australian sixth seed Samantha Stosur, the reigning US Open champion, opens against Czech Clara Zakopalova or a qualifier and she could face a fourth-round matchup with US 10th seed Serena Williams, a 13-time Grand Slam champion.
Williams, a five-time Miami women's champion who has been out with an ankle sprain, will open against either China's Zhang Shaui or Britain's Elena Baltacha.
Belgium's Kim Clijsters is among those who will play in the first round. If the 2005 and 2010 Miami winner defeats Australian Jamila Gajdosova, she will face Germany's 14th-seeded Julia Goerges in round two.
Clijsters is a possible round-of-16 opponent for fourth seed Caroline Wozniacki. The Dane will open against either a qualifier or Czech Barbora Zahlavova Strycova.