OneRepublic frontman Ryan Tedder told Billboard about the song's lyrics: "It's actually about my buried, latent fear of flying and going down in an airplane, having that moment of sheer panic, looking out the window, seeing your life pass before you and somehow finding comfort in the fact that the person next to you is experiencing the same traumatic event."
In an interview with fuse.tv, Tedder said, "The original concept [for the video] was borrowing from the opening scene of Garden State—the plane's going down and all the oxygen masks drop out and everyone's going crazy... We chased that for a minute but realized... It's one thing to watch that kind of video once, but you don't wanna sit there and hit repeat on watching a plane crash."
The music video was released on January 24, 2013. In the video, a group of people are sent a text from Ryan Tedder, of a picture of a wolf and the numbers 11.11.11 at the bottom. The camera follows the group around the city chasing clues that are spray painted on fire hydrants and street signs around the town that will help them guide their way to a secret concert that OneRepublic is holding. The video cuts to scenes of the band performing the song in a dark, smokey room with colored lights surrounding the room with a bunch of fans dancing. There are pictures of owls and foxes being projected around the room which are allusions to the album cover for Native. At the end of the video, there is a fox being projected on Tedder's face. The video was inspired by the movies 12 Monkeys and The Matrix.
The video has over 63 million views as of June 2017. It is one of the top ten most viewed OneRepublic's music videos.
A progressive house version of the song remixed by Swedish producerAlesso was released in certain countries on March 30, 2013, notably Netherlands and Sweden, charting with a version credited to OneRepublic vs. Alesso. "If I Lose Myself" was promoted and released in the United Kingdom and Australia in February 2014. This remix was later featured on both the UK and US reissue of the group's album, Native, as well as Alesso's debut album, Forever (2015).
I haven’t been this happy about a remix I’ve done since "Pressure". I feel like I’ve got everything I want in this record, all what I could wish for musically. I do like the original and I wanted a kick that would preserve the ‘live’ feeling energy you get when you listen to it. I worked on it for like a month, going to the studio everyday, wondering what I was going to do, going backward, forward, trying different beats and drums and basslines, everything. I had an idea but didn’t really know how to make it sound the way I wanted. Then I thought, I’m not going to mess around for ages, I want to give it to them straight away. Sometimes people give just a preview, and you never know when it's coming out. This time I wanted to hear their thoughts immediately because I felt so excited by the record.