The Nicky Henderson-trained Altior is bidding to become only the second three-time winner of the two-mile showpiece, after Badsworth Boy racked up a hat-trick in the 1980s.
However, despite having suffered just one defeat in 21 starts over jumps, the 10-year-old is unlikely to have things all his own way on his return to the Cotswolds, with two formidable rivals taking him on.
Defi Du Seuil has been the star of the division in Britain so far this term, winning each of his three starts for trainer Philip Hobbs and owner JP McManus, including the Tingle Creek at Sandown and the Clarence House at Ascot.
The lightly-raced Chacun Pour Soi beat Defi Du Seuil at the Punchestown Festival - and while he suffered a surprise defeat on his return to action at Leopardstown at Christmas, he bounced back to winning ways at the Dublin Racing Festival.
The eight-year-old is out to provide Willie Mullins with his first Champion Chase success.
The Cullentra handler has also confirmed Min, but he is more likely to run in the Ryanair Chase the following afternoon, as is Henry de Bromhead's A Plus Tard, who was too strong for Chacun Pour Soi over the festive period.
Paul Nicholls is set to saddle last year's runner-up Politologue and Dynamite Dollars, while last year's third Sceau Royal is in the mix for Alan King.
Bun Doran (Tom George), Hell's Kitchen (Harry Fry) and the admirable mare Lady Buttons (Phil Kirby) are the other hopefuls.
Racegoers are being urged not to attend next week's Festival if they are experiencing any of the symptoms associated with coronavirus or if they have travelled through any high-risk countries or been in contact with anyone that has.
A public health notice has been added to the track's latest update on the British Horseracing Authority's administration site.
It reads: "Do not travel to the Festival if: - You have any of the following symptoms - a cough, a high temperature or shortness of breath AND - You have been to or transitted through the high-risk countries, or been in contact with anyone that has, in the last 14 days.
"To protect yourself and others please do not travel and call NHS 111 (GB) or HSE 112 (Republic of Ireland) for expert advice.
"These measures are being taken in order for us to safeguard everyone's health and wellbeing during the current public health situation.
"Thank you for your understanding. For more details, please visit gov.uk/coronavirus."
The Betfair market surrounding the possibility of the Festival's cancellation has attracted plenty of attention in recent days, with £2.4 million traded, but the fixture remains odds-on to go ahead at 1.38 (4-11).
However, the firm has opened the market on the likelihood of next month's Grand National taking place, with a small amount traded so far, just under £4,000 at 11.10am, favouring the meeting being called off.
Betfair spokesman Barry Orr said: "The odds on Cheltenham seem to have stabilised at around 2-5 which is encouraging, but since we went up with the Aintree market it's been odds-on not to take place and the ramifications that could have for the racing world are wide reaching."