Another boy was left in critical condition at the hospital.
The crash was reported in the area of Avenue G between 30th Street East and 20th Street East just after 9 a.m.
Authorities say one woman - the driver of the car - was declared dead at the scene and one female adult passenger and two boys were declared dead at the hospital.
The crash involved a large truck and a black sports car. The car held five people - two women and three boys, ranging in age from 5 to 11.
The two older boys died and a younger one was fighting for his life in critical condition at the hospital.
The male driver of the truck suffered minor injuries.
The cause of the crash remains under investigation.
Authorities said earlier this week they have seen a sharp rises in fatal crashes in the Antelope Valley. They attributed the increase to empty roads during the pandemic leading to more speeding. CHP and the sheriff's department say they have been cracking down on speeding.
It is not known whether speed was a factor in Friday's crash.
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