Ashleigh Barty and Nick Kyrgios won't be there but COVID-19 hasn't deterred Alex de Minaur, who has committed to lead Australia's 10-strong assault on the US Open singles events.
Ranked 26th in the world, de Minaur is expected to be seeded 21st in the men's event when the New York grand slam gets under way in a strict biosecurity bubble on Monday.
The Spain-based Australian No.1 joins 2018 quarter-finalist John Millman, Davis Cup teammate Jordan Thompson, fellow Sydneysiders James Duckworth and Chris O'Connell and US Open main-draw debutant Marc Polmans in the 128-man field.
With world No.1 Barty and former Flushing Meadows champion and new mum Samantha Stosur both opting out, Ajla Tomljanovic will lead the women's charge.
Maddison Inglis, Astra Sharma and Lizette Cabrera are also in a women's draw depleted by the withdrawals of six of the world's top 10 players.
Along with Barty, world No.2 and reigning Wimbledon champion Simona Halep, world No.5 Elina Svitolina, sixth-ranked titleholder Bianca Andreescu, world No.7 Kiki Bertens and world No.8 Belinda Bencic are also bypassing the slam.
World No.3 Karolina Pliskova is set to be the women's top seed ahead of Australian Open champion Sofia Kenin and 23-times major winner Serena Williams.
World No.1 Novak Djokovic headlines a men's draw that doesn't contain either defending champion Rafael Nadal or five-times winner Roger Federer for the first time since 1999.
De Minaur, who lost to big-hitting German Jan-Lennard Struff in the opening round in Cincinnati this week in his first match since February, reached the final 16 last year in his best run yet at a grand slam.
Six other Australians are playing doubles in New York, including the 2020 Australian Open runner-up pairing of Luke Saville and Max Purcell.
Davis Cup star John Peers is partnering Kiwi Michael Venus.
Ellen Perez and Storm Sanders are teaming in for the women's doubles, as are Arina Rodionova and Sabrina Santamaria.
Dylan Alcott will contest singles and doubles in the quad wheelchair competition.
The US Open seedings are due out on Thursday, with the draw taking place on Friday AEST.