Top-ranked Novak Djokovic made a strong start Friday in his quest for a third consecutive Miami Open title while Roger Federer's expected return from a two-month layoff was over before it started.

Djokovic, seeking his sixth Miami crown overall and the first "three-peat" since Andre Agassi in 2001-2003, opened by defeating Britain's 87th-ranked Kyle Edmund 6-3, 6-3 in the ATP and WTA hardcourt event.

"I had a solid performance," Djokovic said. "I started with the right intensity and good focus. I had slight ups and downs. I'm pleased. I'm looking forward to the next one."

Djokovic, who captured his 11th Grand Slam singles crown at the Australian Open two months ago, will face Portugal's Joao Sousa in the third round Sunday as he tries to add to a 2016 trophy haul that also includes Doha and Indian Wells.

The 28-year-old Serbian is 23-1 this year and has 25 of his past 26 Miami matches, including 11 in a row.

But third-ranked Federer, a 17-time Grand Slam singles champion who underwent left knee surgery last month, withdrew from the tournament just hours before his match, citing a stomach virus.

"I have not felt great for a few days and unfortunately it got worse in the last 24 hours," Federer said. "I was really excited to have my comeback in Miami but I am in no condition to play. I tried to warm up this morning but it was clear that I could not compete."

The 34-year-old Swiss legend missed the event for the third time in four years. He won at Miami in 2005 and 2006 but has not reached the final since.

Federer has not played since losing to Djokovic in the Australian Open semi-finals two months ago. The next morning, Federer suffered a torn meniscus while preparing to bathe his children.

Federer had not expected to be ready in time to play at Miami but recovered well from the operation and said he was excited for the opportunity.

"It's good it's a stomach problem and not the knee, so it's not a big deal," said long-time Federer rival Rafael Nadal.

- Pained Del Potro exits -

Federer was replaced by 58th-ranked lucky loser Horacio Zeballos, who made the most of his chance by defeating Argentine compatriot Juan Martin Del Potro 6-4, 6-4.

"I was sitting in the locker room playing chess and watching others playing when they told us the news. I was really happy," said Zeballos.

"I was so relaxed. I played great. I knew I was playing Juan Martin and he had more pressure than me so I played relaxed."

It was only the third event for 366th-rated Del Potro, the 2009 US Open champion, in his comeback following left wrist surgery last year and he struggled with pain.

"I was suffering a little bit," Del Potro said. "It was worse than my first match but I hope nothing dangerous.

"This is a long road to get better and play tennis again. For me, it's like a surprise when I win a match. I'm trying to deal with the pain. I'm suffering but I'm playing tennis and that's good."

- Kerber, Muguruza advance -

Reigning Australian Open champion Angelique Kerber and Spanish fourth seed Garbine Muguruza, last year's Wimbledon runner-up, reached the third round.

German second seed Kerber cruised past Czech Barbora Strycova 6-1, 6-1 while Muguruza battled for two hours and 45 minutes before subduing Slovakia's 54th-ranked Dominika Cibulkova 6-7 (3/7), 6-3, 7-5.

Next up for Kerber, whose best Miami showing was a 2014 quarter-final run, is 108th-ranked Dutch qualifier Kiki Bertens. Muguruza will meet US wildcard Nicole Gibbs.

Spanish sixth seed Carla Suarez Navarro was ousted by American CoCo Vandeweghe 6-4, 6-2 while Swiss seventh seed Belinda Bencic retired with a lower back injury trailing Czech Kristyna Pliskova 4-1.

Tenth seed Venus Williams, a seven-time Grand Slam singles champion and three-time Miami winner, was eliminated by Russian qualifier Elena Vesnina 6-0, 6-7 (5/7), 6-2.

"I couldn't afford many errors and she was on," Williams said. "It's tough to play your best tennis against an opponent so inspired that you can't get into the match."

Vesnina, ranked 96th in the world, next faces British 23rd seed Johanna Konta, who defeated Montenegro's 51st-ranked Danka Kovinic 6-4, 6-2 and is the top-seeded remaining player in her eighth of the draw.