The blaze broke out around 5am this morning at the residence in Villafranca de Ebro near the northern city of Zaragoza.
More than 80 people were inside at the time, regional governors have said, Daily Mail reported.
The home has been named locally as Jardines de Villafranca, a retirement complex comprised of three adjoining buildings that stands alone on a large plot of land.
Firefighters are still at the scene alongside police, Civil Protection and social workers and paramedics.
The blaze has since been extinguished but it is not yet clear why it started.
The fire sparked a massive response from emergency services with firefighters, paramedics and members of Spain's Civil Guard descending on the scene as day broke.
Psychologists and social workers were also sent to the scene to provide support to the victims' families and affected residents.
Firefighters managed to extinguish the flames in the early hours of the morning, but the damage was already done. Ten residents were reported dead, with an eleventh in critical care at the nearby Miguel Servet hospital.
Dozens of other residents were successfully evacuated but several needed treatment for smoke inhalation and other minor injuries. As an investigation was launched into the cause of the fire, top officials flocked to the scene.
Minister of the Interior for the regional government, Roberto Bermudez de Castro, and the manager of the Institute of Social Services (IASS), Angel Val, both travelled to assess the situation.
A preliminary report on the cause of the fire is expected in the coming hours, the report added.
MA/PR