Exactly one year prior to the beginning of DearS, humanity made unprecedented contact with extraterrestrial life. Forced to crash land into Tokyo Bay when, en route to their home planet of Thanatos, their spacecraft breaks down, 150 humanoid aliens arenaturalized into Japanese society and affectionately nicknamed "DearS"; a portmanteau of the words "Dear" and "Friends".

Takeya Ikuhara is a temperamental seventeen-year-old Japanese student attending the fictitious Koharu High School with a strong prejudice against the DearS. Due to a childhood scare, he believes that the aliens are fake, worthless beings that have generated nationwide overhype and are secretly plotting to take control of Earth.

On his way home from school he discovers a homeless DearS who, after fainting and much to his annoyance, he feeds and shelters in his apartment. The girl, who he nicknames Ren, is infantile and friendly, and grows obsequious and dependent upon Takeya, a responsibility he tries to disassociate himself from. Her oblivious tenacity keeps her around, however, and over time, realizing Ren's genuine care and empathy for him, Takeya has a change of heart. Unfortunately, because Ren is deemed defective, DearS headquarters orders her arrested.