One year prior to the beginning of the story, mankind made its first contact with an alien species, when a malfunctioning alien spacecraft made an impromptu crash-landing in Tokyo Bay. The aliens on board the UFO are human-like and remarkably beautiful, and are soon affectionatly nicknamed "DearS" by their human hosts, which means "Dear friends from outer space"; as extraordinarily kind and gentle as they are lovely, the DearS are a slave race in actuality, seeming to thrive as individuals and as a species by making others happy; as they are unable to return home, the small community of DearS attempts to integrate themselves into human society, concealing their status as a slave race from the public due to concern over the fact that humanity does not agree with slavery.

The main plot follows the story of Takeya Ikuhara, an average high school student in the fictitious Koharu precfecture, and how his life is turned on its head, due to the appearance of a beautiful and apparently defective DearS he calls "Ren", who, after Takeya saves her life and nurses her back to health and teaching her the ways of the human society, promptly becomes attached to him and moves into the closet of his apartment, declaring herself his slave and him her master.

As the story progresses, Takeya finds himself becoming surrounded by several more DearS along with his near-constant companion Ren. The cast is further-expanded with the introduction of Takeya's family and friends. The focus shifts to follow the progression of Ren's growth as a person and learning about the world around her, Takeya's overcoming of his suspicion of the DearS' true intentions by his acceptance of Ren and his attempts to keep the somewhat naive DearS out of harm's way, and the machinations of parties, both DearS and human alike, in either progressing or halting the evolution of Takeya's relationship with Ren into something more serious than an unlikely master-slave bond - the culmination of which, along with a shocking revelation as to the true nature of the clueless "Zero Number", will ultimately determine the fate of mankind as a Whole.