It happened Monday afternoon in the 23400 block of the North Freeway.
A black sedan was either stopping or had already stopped in traffic when it was struck from behind by a red Mustang, according to the Harris County Sheriff's Office.
Deputies said two children, ages 11 and 13 were taken to Memorial Hermann hospital by Life Flight, but later died. There was no word on the conditions of the three adults who were transported by an ambulance.