The collision was reported just before 10 p.m. and forced the California Highway Patrol to shut down all southbound lanes of the freeway at Sunland Boulevard.
A person was pronounced dead at the scene, according to the Los Angeles Fire Department.
Fire officials said four females - ages 7, 19, 22 and 42 - were taken to hospitals in fair or serious condition.
Video from the scene showed a red SUV with extensive front-end damage and another damaged vehicle stopped in the middle of the roadway.
Traffic on the southbound 5 was brought to a standstill as officials investigated the crash. The cause of the collision is unknown.
One lane reopened just before 11:20 p.m. It's unclear when all lanes will reopen.