The heavy rockers performed four songs, including versions of Led Zeppelin's Stairway to Heaven and the Beatles' In My Life, at the Club Nokia gig in Los Angeles and told guests they were thrilled to be able to play.
Frontman James Hetfield said, "We're here to celebrate life, man. Are you alive? It feels good most of the time. Sometimes not as much, but when we get together like this it feels a lot better."
Bandmate Kirk Hammett revealed the night was extra special because it gave him and his bandmates the chance to honour their friend and mentor Osbourne, who was handed the Stevie Ray Vaughn Award by longtime pal Joe Walsh.
He told Rolling Stone, "MusicCares is a great organisation and they've helped out a lot of our friends. And Ozzy Osbourne has done so much for us. This is one small way we can say thank you to him."
Bassist Robert Trujillo added, "I don't know if we'd be doing what we do if there wasn't an Ozzy and a Black Sabbath. We grew up playing those songs and the first time I picked up the bass and started getting into it, I was playing Iron Man or Sweet Leaf. He's our brother and this organisation has really helped save his life and keep him with us and more powerful than ever."
Osbourne closed his own tribute gig by taking the stage with his band, Slash and Jane's Addiction guitarist Dave Navarro for a set that featured hits like Crazy Train and Black Sabbath's Paranoid.
The MusiCares Foundation, Inc. was created to give musicians a place to turn in times of financial, personal, or medical crisis.
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