Novak Djokovic faces the daunting prospect of possibly having to beat Roger Federer and Rafa Nadal to win the US Open for the first time and end the year as the world number one.

The Serbian has already won this season's Australian Open and Wimbledon titles and is the overwhelming favourite to win the last Grand Slam of 2011, starting at Flushing Meadows on Monday, to wrap up the top spot for the end of year rankings.

But a niggling shoulder injury that forced him to quit last weekend's Masters final in Cincinnati, has raised questions about his fitness, especially with his foes lurking ominously at the business end of the tournament after the official draw was conducted in New York on Thursday.

Djokovic was drawn to launch his tournament against an as yet unknown qualifier but if results go according to the rankings, the top seed will face a tricky last weekend, when the semi-finals and final will be played on successive days.

His projected semi-final opponent is five-time US Open champion and third seed Federer, who faces Colombia's Santiago Giraldo in the first round.

If Djokovic can beat the most prolific male Grand Slam winner of all time, his opponent in the final could be either Nadal, who beat him in last year's final, or the in-form Briton Andy Murray.

"Last year was a very emotional time for me, because I completed all my Grand Slams," Nadal said at Thursday's draw after the second seeded Spaniard was drawn to face Kazakhstan's Andrey Golubev first up.

"It was very tough but I played some of my best tennis in the final (against Djokovic) and I known I can do well."

Djokovic is not the only top player with concerns. Nadal has been battling blisters and Federer has not won a Grand Slam in nearly two years.

Former world number one John McEnroe, speaking on American television network ESPN, said he was tipping Murray to win the men's singles title.

The fourth-seeded Scotsman is the only player in the top four who has yet to win a Grand Slam but has been in great form during the US hardcourt season. His first round opponent is Somdev Devvarman of India.

"The hungriest guy out there should be Andy Murray," McEnroe said. "This is his best chance ever to win a major."

McEnroe said he would be surprised if anyone outside the top four won the title but he nominated towering Argentine Juan Martin Del Potro as the most likely to cause an upset.

Del Potro won the US Open two years ago, beating Federer in the final, but was unable to defend his title last year because of an injury. He makes his return this year against Italian Filippo Volandri.

The return of American Serena Williams provided an element of suspense and intrigue to the women's draw, weakened by the absence of injured Belgian Kim Clijsters, who won the title the past two years.

Williams, the dominant figure in women's tennis over the past decade, has won the US Open three times but the former world number one was relegated to 28th seed after her ranking tumbled during her long absence from the game, because of health problems.

The 29-year-old American has won two tournaments since returning and was lurking as one of the dangerous floaters in the draw. She was paired to meet Serbia's Bojana Jovanovska in the opening round with fourth seed Victoria Azarenka of Belarus waiting in the third round.

Williams fared well in the draw. If results go according to seedings, she could face Italy's Francesca Schiavone in the quarter-finals and world number one Caroline Wozniacki in the semis.

The Dane was a runner-up in New York two years ago but has yet to win a Grand Slam and could faces a tricky quarter-final herself, against China's French Open champion Li Na, after opening against Nuria Llagostera Vives of Spain.

Russia's Maria Sharapova, seeded third, was drawn to face Britain's Heather Watson in the first round ahead of a possible quarter-final against Petra Kvitova, the Czech who beat her in this year's Wimbledon final.

Russia's Vera Zvonareva, the world number two and second seed, was pitted against undecided qualifier in the same quarter of the draw as Venus Williams, who was unseeded after a long layoff.