Set in Catalonia, Painless weaves two stories: in one, starting during the Spanish Civil War and running through to the '60s, an asylum attempts to rehabilitate children who feel no pain, by teaching them physical suffering. In the second, in the present time, a brilliant neurosurgeon who needs a bone marrow transplant, discovers this dark past when he searches for his biological parents.

Inspired by real events, the story centers around a family in the 70s who settles in the Madrid neighborhood of Malasaña where their new house will become the worst of their nightmares.