The Lost creator, who redrafted Jon Spaihts's original script for the first film, said that potential scheduling prevented him from joining the project.
Lindelof recently worked on the screenplay for Star Trek Into Darkness and has a collaborative project with Brad Bird and a TV venture on the horizon.
"I'm usually very single-minded creatively. I can only be working on one thing at a time. So I said to [director Ridley Scott], 'I really don't think I could start working on this movie until I do this other stuff," he told Collider.
"And I don't know when the other stuff is going to be done'. And he was like, 'Well, okay, it's not like I asked you anyways'.
"He and I are on excellent terms and it was a dream come true to work with him. But much to the delight of all the fanboys, I don't see myself being involved in Prometheus-er."
Michael Fassbender and Noomi Rapace are expected to reprise their roles for the Prometheus sequel, which is rumoured to be titled Paradise and arrive in either 2014 or 2015.
Watch Rafe Spall discuss Prometheus with Digital Spy below: