Game Changer appeared at Southampton Hospital during the first wave of the pandemic.
Now the anonymous graffiti artist is auctioning the original canvas to raise funds for the NHS, with the reproduction of the work remaining in the hospital.
The hand-painted image shows a young boy playing with superhero dolls.
While Batman and Spiderman are discarded in a bin, the child clutches a figure of a masked nurse wearing a cape.
Christie’s said that the image “offers an image of hope” and represents a “personal tribute to those who continue to turn the tide of the pandemic”.
Banksy’s Game Changer was a beacon of light for the staff and patients at Southampton General Hospital and it was the artist’s wish to then auction it with proceeds benefiting the NHS
Katharine Arnold, co-head, post-war and contemporary art, Europe at Christie’s, said: “Game Changer is a universal tribute to all those fighting worldwide on the front line of this crisis.
“At a time when we can dare to hope once more, and look at life beyond the pandemic, it is important to reflect on the many symbols of strength and hope we have seen internationally since the beginning of 2020.
“Banksy’s Game Changer was a beacon of light for the staff and patients at Southampton General Hospital and it was the artist’s wish to then auction it with proceeds benefiting the NHS.
“The work pays tribute to the strength and resilience of those who have demonstrated true leadership throughout the pandemic, the staff of our vital NHS.”
When first unveiled, the picture was accompanied by a note: “Thanks for all you’re doing. I hope this brightens the place up a bit, even if it’s only black and white.”
Game Changer will be seen outside the hospital for the first time, from the window at Christie’s headquarters in London from March 8 to 15.
Game Changer will be offered at auction in Christie’s 20th Century Art Evening Sale on March 23, with a pre-sale estimate of £2.5 to £3.5 million.