Crews were called out to the 400 block of Feather Drive around 3 a.m.
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Firefighters found smoke pouring from the basement of the home.
A 13-year-old, an 18-year-old, a 25-year-old and a 44-year-old suffered from smoke inhalation and were taken to Christiana Hospital for treatment.
The 18-year-old and the 25-year-old were then transferred to Crozer Medical Center where they are in critical condition.
The 13-year-old and the 44-year-old were treated and released.
The Delaware State Fire Marshal's office is investigating.
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