Aguilera collaborated with several songwriters for Bionic, including Australian singer-songwriter Sia on this track. She told PopEater why she chose to work with other artists for the album. Said Aguilera: "The artists I collaborated with on this album are ones I have been fans of for years. When I was pregnant with Max, I was listening to a lot of Sia, M.I.A., etc. My husband said, 'Why don't you ask them to collaborate?' That thought never even crossed my mind, but I am so glad I did it. They were amazing to work with and really allowed me to do my thing and they did theirs, so there is a great mix of both sounds. Each of us had something unique to bring to the table. Sia also taught me to appreciate the imperfections in my voice and that is where the sound on 'You Lost Me' came from.
Aguilera performed this song on the 2009 American Idol season 9 finale show.
The song's music video was directed by Anthony Mandler. The director also wrote the concept for the clip, which features a series of connected vignettes highlighting a devastated Aguilera trying to deal with a doomed romance. "From the first keys of the opening of the track, we know that we are about to watch something that is going to move and transform us," Mandler told PopEater. "In the end, we've traveled through Christina's world. One that is physical, mental and spiritually charged. Nothing is what it seems. Everything is fractured and evolving, falling away... fragile."
The song was released as Bionic's third single on July 6, 2010 in the United States. However, it was not commercially successful and became Aguilera's first single to not chart on the Billboard Hot 100.