Upon entering the prestigious all-girls Seiran Academy, 16-year-old Nanako Misonoo expects a bright future. Instead, the unfortunate girl is pulled into a web of deceit, misery, and jealousy. Furthermore, she is selected as the newest inductee of the Sorority, an elite group whose members are envied by the entire school. Lacking the grace, wealth, or talent of the other members, Nanako quickly provokes the anger of her jealous classmates—particularly the fierce Aya Misaki. To manage her increasingly difficult school life, Nanako reflects on her past through letters to her former teacher, Takehiko Henmi, whom she affectionately calls "onii-sama" (big brother). She also finds solace in her four closest friends: her childhood friend Tomoko Arikura, the sociable but erratic Mariko Shinobu, the troubled musician Rei Asaka, and the athletic tomboy Kaoru Orihara. An impassioned drama concerning the hardships of bullying, Oniisama e... chronicles a young girl's harsh life at her new school, as she endures cruel rumours, heartless classmates, and countless social trials.