Donors at the event — touted as one of the largest of its kind – can meet players, join a bone marrow registry and enjoy live entertainment.
A new Honda CRV will be given away at 5 p.m.
A wellness zone will offer screenings for high blood pressure, sleep apnea, diabetes and body mass index.
Experts on genome sequencing will also be on hand.
The event will conclude with a fashion show featuring Chargers players and their families, including receiver Keenan Allen, cornerback Derek Cox, tackle D.J. Fluker and linebacker Manti Te’o.
Alumni expected to attend throughout the day are Hank Bauer, Rolf Benirschke, Darren Bennett, Jim Laslavic and Billy Ray Smith.
The drive started in 1979 when Benirschke, a popular placekicker at the time, developed ulcerative colitis and underwent two surgeries to remove his large intestine, which required about 80 pints of blood.
Team officials called the San Diego Blood Bank and asked if they could collect donations, and the next day, about 1,000 fans showed up at the stadium and donated nearly 300 pints of blood.
“It really started around the love affair that the city had with the team,” Benirschke said at the 2011 blood drive, when more than 1,000 pints were collected.
“I just happened to be the one that was sick. Some people waited four hours to give blood.”
The blood bank expects 2,500 people to attend this year’s blood drive, which will run from 10 a.m. to 5 p.m.