Andy Murray is top seed after stepping in at LA Open
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," said tournament director Bob Kramer. "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, although he has tasted success in California previously after tournament victories in San Jose in 2006 and 2007.
The Scot will be making his first appearance since Wimbledon in June, where home hopes of a long-awaited British victory were high until he was defeated just one match from the final by the eventual winner Rafael Nadal.
Big-serving American Sam Querrey, who won last year's title, has been seeded second with Cypriot Marcos Baghdatis third and Spaniard Feliciano Lopez fourth.