Sam Smith recorded the single in Los Angeles with John Legend earlier this year.
They will perform the ballad during Comic Relief: Face the Funny on Friday, March 13, on BBC One.
The one-off performance will be broadcast live from the London Palladium.
A digital download of the special track has been released ahead of their performance.
Sam Smith said: “Lay Me Down holds a very special place in my heart.
“Not only did I perform it at the Brits, I’m now going to perform it live on the Red Nose Day show with the extremely talented John Legend.”
John Legend said: “Sam is such a talented artist. We’ve been looking forward to working together for a while now.
“I’m so glad we could collaborate on such a great song and for such a great cause.”
All the profits from the sale of Lay Me Down will go to Comic Relief.
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