The train cars were carrying coal and contained no hazardous materials, The Baltimore Sun reported.
The victims were found in the wreckage of 21 cars that derailed or overturned in Ellicott City around midnight. The train was comprised of 80 cars.
Two persons operating the train were not injured, police said.
Vehicles parked nearby were crushed by some of the derailed rail cars.
Neither the identities nor the genders of the victims have been released.
The cause of the derailment is being investigated by a CSX team.