Firefighters arrived at the 13400 block of Saticoy Street around 12:30 a.m. It took nearly two hours for about 150 firefighters to get a handle on the fire.
Investigators believe the blaze erupted at a wood pallet warehouse located next door to the shelter and quickly spread.
Thirty residents, including several children, who were asleep when the fire started were awakened by shelter staffers and fled from the burning building.
No injuries were reported. The cause of the blaze is under investigation.
Damage to the facility which serves as the rescue mission's operation center is extensive. Officials say the facility and its homeless residents lost virtually everything, including food.
"This is our home. There's nine to 10 families here, we all have children," said shelter resident Nancy Arias in tears.
"When I say we've lost everything, that means diapers for families like Nancy's family. That means hygiene supplies. That means everything from soap and toothbrushes, clothing," said San Fernando Valley Rescue Mission Executive Director Wade Trimmer.
The facility serves more than 800 people in need every month. In addition to the dormitory for families, the mission lost its food pantry, thousands of dollars worth of donated clothing, and six trucks used to deliver food to needy families in the community.
The Red Cross has set up a shelter at the Branford Recreation Center, located at 13310 Branford Street in Pacoima, to assist the people affected by the fire.
The mission desperately needs cash as well as clothing and household supplies to continue its work. Anyone who would like to help or donate items was urged to contact the San Fernando Valley Rescue Mission at (888) 937-4448. Donations may also be made at www.sfvrescuemission.org.