A tendon injury has forced connections to bring Native River's season to a premature end.
The 2018 Cheltenham Gold Cup winner was found to have the problem by trainer Colin Tizzard, ruling him out of this year's contest sponsored by Magners.
He will also miss the Randox Health Grand National, a contest he became second favourite for recently after being given what looked a competitive weight.
Garth Broom from owners Brocade Racing said: "It’s a bit of a blow - a suspensory behind his knee, so that means he’s finished for the season, unfortunately.
" There are a hell of a lot more downs than there are ups, unfortunately.
"You plunge from a great height to a great depth sometimes.
"It's not a life-threatening thing. That's the main thing.
"It could have been worse news.
"He’s done us really proud he doesn’t owe us anything but there was the feeling this was our last live chance in the Gold Cup."
After finishing fourth in last year's contest behind Al Boum Photo, the Colin Tizzard-trained chaser returned this season and raced in blinkers, headgear he is unbeaten in from two starts.
He secured a third Denman Chase earlier this month and was thought to be back to his best.
Yesterday it was revealed Mark Walsh had picked up the ride on 6/1 shot Delta Work.
Last year's winner Al Boum Photo will be given an away day by trainer Willie Mullins to complete his preparation, the Irish trainer reported earlier.
He said he expects 2019 first fence faller Kemboy to put in a big performance if the ground dries sufficiently.
