Serbian Djokovic pulled out of the ATP Tour event late on Friday night, citing personal reasons, organisers said.
Czech Radek Stepanek, the 2007 champion, also withdrew on Friday due to a knee injury.
"It's certainly disappointing to lose players like Novak and Radek," tournament director Bob Kramer said in a statement.
"We were looking forward to Novak making his debut in LA, but we're very fortunate that Andy Murray, another top-five player, will be able to join us."
Murray, who has been given a wild card entry, will be making his first appearance at the event held at the LA Tennis Center.
(Writing by Mark Lamport-Stokes in Laguna Seca, California; Editing by John Mehaffey; To query or comment on this story email email@example.com)