Burnside shopping centre management said a towering, century-old gum tree in the centre was now dead and would be removed this weekend.
Much has been spent on trying to save the river red gum since it was enclosed by stores and a canopy when the shopping centre was expanded in 2011.
Pat Cohen, director of the Cohen Group which owns the Adelaide eastern suburbs shopping centre, said the tree now had to go.
"According to our experts it is beyond [help], it will not survive so we've made a decision to remove it straight away," she said.
"[It's a bit like] a favourite member of the family that's been in intensive care for a long time and the doctor has to finally come to a decision, brain dead, remove all the things so that's what we're doing.
"So over the next two nights the tree will be gone."
She said no decision had been made on what would replace the tree, but there were lots of ideas.
Ms Cohen said the area would become safer for people to enjoy a coffee.
The Cohen Group was required to retain the tree as part of its plan to extend Burnside.
Ms Cohen said millions of dollars had been spent on trying to retain the tree and then keep it alive inside the shopping centre.
She said the problem had been ensuring the tree got enough ultraviolet light.
As part of the failed efforts to save the tree, more air-conditioning vents and a misting system had been installed and the tree had been injected with nutrients.
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