The series takes place in the year 2196, where the Earth is in a war with a race of alien invaders called the "Jovian Lizards". To combat it, a company called Nergal designs a powerful space battleship, the ND-001 Nadesico. The main problem with the Nadesico is the crew. While it consists of the top civilian experts in their fields, these individuals tend to have "some slight personality disorders".