The final grand slam of the year, the US Open at Flushing Meadows, will be devoid of some of the finest talents in the men's game - and other star names may be added to the growing list.
With another top-10 player, Kei Nishikori, having pulled out on Wednesday, we take a look at the remarkable list of those who will miss out and those in danger of joining them...
OUT - NOVAK DJOKOVIC (Rank: 5; Best US Open performance: Winner - 2011, 2015)
It has not been a good year for Djokovic, whose air of invincibility has well and truly evaporated.
The 12-time grand slam champion decided last month that he would no longer battle on with a persistent elbow problem.
It forced him to withdraw from his Wimbledon quarter-final match against Tomas Berdych.
OUT - STAN WAWRINKA (Rank: 4; Best US Open performance: Winner - 2016)
Knee surgery put paid to Wawrinka's hopes of defending his US Open crown.
The Swiss had been enjoying a strong year in the slams, progressing to the Australian Open semi-finals and losing in the final of the French to a resurgent Rafael Nadal.
As with Djokovic, fitness woes hit at the All England Club, where he required ice on his knee in a first-round loss to Daniil Medvedev.
Not the place I wanted to be but 2nd surgery went well! That's mean I can start my preparation... 2018 see you soon! Thanks to all- pic.twitter.com/wGgrZpiwa6-- Stanislas Wawrinka (@stanwawrinka) August 15, 2017
OUT - KEI NISHIKORI (Rank: 9; Best US Open performance: Finalist - 2014)
The Japanese called time on his 2017 season after tearing a tendon in his right wrist.
Nishikori reached the semi-finals at Flushing Meadows last year, but will not be back there this time around after suffering the injury during practice in Cincinnati.
It brings a premature end to a campaign that yielded no titles for the 27-year-old, who made it to the last eight at the French Open.
DOUBT - ANDY MURRAY (Rank 1; Best US Open performance: Winner - 2012)
Murray will soon be replaced by Nadal as world number one, the 30-year-old Brit having struggled for form and fitness.
A hip issue has blighted his season and Murray is far from certain to compete in 2017's final slam, having withdrawn from the Western & Southern Open.
The US Open was the scene of Murray's maiden major triumph five years ago.
DOUBT - ROGER FEDERER (Rank 3; Best US Open performance: Winner - 2004, 2005, 2006, 2007, 2008)
It is not part of the script in Federer's stunning renaissance story that he should now be failed by his 36-year-old body.
But the Swiss maestro was another withdrawal in Cincinnati, having tweaked his back at the Rogers Cup.
He lost in the final of that tournament, his only defeat in a title match this season, during which he has won the Australian Open and Wimbledon.
Thanks so much for all the birthday wishes from around the world! Feeling the #36 #2ndTime18-- Roger Federer (@rogerfederer) August 9, 2017
DOUBT - MILOS RAONIC (Rank 10; Best US Open performance: Fourth round - 2012, 2013, 2014)
The Rogers Cup claimed another victim in the shape of home hope Raonic.
He suffered a wrist injury in a straight-sets loss to Adrian Mannarino.
Of all the confirmed and possible absentees, Raonic's record at the US Open is the least remarkable.
DOUBT - MARIN CILIC (Rank 6, Best US Open performance: Winner - 2014)
Cincinnati tournament organisers might be forgiven for taking it personally, as reigning champion Cilic was another to give that one a miss.
He won his maiden ATP Masters 1000 title there, but an adductor injury sustained during his Wimbledon final loss to Federer remains problematic.
Cilic's only slam victory came at the US Open in 2014.