The event, now in its 12th year, begins in Balboa Park, runs through Hillcrest and downtown San Diego, makes its way around Mission Bay and concludes at the Marine Corps Recruit Depot.
There will be more than 40 live bands performing on stages set up at each mile along the race course, thousands of cheerleaders, themed water stations and a post-race concert.
Hundreds of joggers donning Elvis Presley costumes are also part of the "Rock `N' Roll Marathon" tradition.
Along with all of the fun will be a slew of road closures.
The bulk of road closures begin at 5 a.m. and streets will be intermittently shut down and reopened as the runners make their way along the marathon course, according to organizers.
Southbound state Route 163, between Interstate 805 and downtown, will be closed from 2 a.m. until noon. There will also be several freeway off-ramp closures on interstate 5, Interstate 8 and state Route 163.