The October 21 event has drawn 60 initial entries, but the Michael Bell-trained Big Orange and Aidan O'Brien's Order Of St George are the two key names after fighting out a thrilling finish for the Gold Cup at Royal Ascot.
Big Orange prevailed by a short head in June and has since finished second when chasing a third victory in last week's Goodwood Cup, when he finished just a length and three-quarters behind Stradivarius, who is also entered on Champions Day, despite conceding 13lb.
Bell said: "He's having an easy time for two or three weeks now as he lost a lot of weight, he lost 18 kilos and he was a tired horse after Goodwood.
"He ran a fantastic race. I was hugely proud of him and he absolutely gave his all. It was a very tough ask trying to give all that weight away to a three-year-old but he fell on his sword."
Big Orange could take in the Irish St Leger en-route to Ascot, with O'Brien considering a similar plan for Order Of St George, who finished fourth on Champions Day last year having previously claimed third in the Prix de l'Arc de Triomphe.
The Ballydoyle handler said: "The plan with Order Of St George is we might start him off in an Irish Leger trial and then go for the Irish Leger first, but it's definitely a strong possibility he'll go to Ascot.
"Last year was one of those races that didn't work out for him, but he's a big, hardy individual, physically and mentally. He's had a break since he finished second at Ascot but he's perfect and not far away from running again now."
Willie Mullins has entered three, with Max Dynamite, Renneti and Wicklow Brave bidding to give their handler a first Champions Day success.
Other notable entries include 2015 victor, Flying Officer, last year's winner Sheikhzayedroad and Hardwicke Stakes hero, Idaho.