The half-hour show is written and produced by Mike White and stars Dern as a self-destructive woman who has a spiritual awakening after suffering a nervous breakdown.
"I am stoked to finally party with HBO," White said.
He added: "I feel lucky to have been given this opportunity to make something original, heartfelt and weird."
Whit also directed the series pilot.
Enlightened is expected to premiere on HBO this summer.