Afflicted by an incurable illness, Yuuji Kaidou dreams of a better future and decides to rely on a cryogenic technology that allows him to sleep until a cure is found. Unfortunately for the young man, he awakens surrounded by man-eating monsters and is saved in extremis by a group of soldiers who use large combat machines to slay these ruthless creatures.

Yuuji learns from Marlene Angel, the leader of the soldier team that saved him, that an alien species known as BLUE had invaded Earth decades ago, leaving humanity on the brink of extinction. Initially overwhelmed by the nightmarish reality, Yuuji joins the resistance against the BLUE. But in order to prevail over these monstrosities, he will need more than just determination if he wants to make a difference in the battle to save mankind.

Blue Gender was released on DVD in North America by Funimation Entertainment in eight volumes from October 16, 2001, to January 28, 2003. The publisher re-released the series on Blu-ray and DVD on June 21, 2011.