Both heavyweights come in well under the 265-pound limit, with Velasquez (9-0) at 249 pounds and Dos Santos (13-1) 10 pounds lighter at 239.
The Southern California crowd drowned out Velazquez's comments. Dos Santos simply said, "Get ready for a war."
The UFC on Fox event is the first of a seven-year deal signed earlier this year. This hour-long show will feature just the heavyweight fight. UFC president Dana White has said future shows will likely last 90 minutes and feature multiple fights.
Although it won't be televised, a lightweight bout between former WEC champion Ben Henderson and Clay Guida will draw a lot of attention. During Friday's weigh-in, UFC commentator Joe Rogan declared the winner would be next in line to face champ Frankie Edgar.
"This will determine who gets the next shot at the lightweight strap," Rogan said.
Both Henderson and Guida came in right at the 156-pound weight limit.
The event will be held at the Honda Center in Anaheim, Calif., the same venue in which Velasquez claimed the title with a win over Brock Lesnar in October 2010.
Brett Okamoto covers mixed martial arts for ESPN.com. Follow him on Twitter.