Megumi hates living in the small village of Sotoba. She dreams of graduating from high school and moving to the city. Only two things hold her interest in the village, the giant European Mansion that was recently built atop a hillside and the boy Yuuki Natsuno.

The owners of the mansion, the Kirishiki's, arrive under the cover of darkness. Megumi marches up their mansion with fantasies of being adopted.

Hours later Megumi has failed to return home with the sun set the villagers begin searching the woods for her. They find her lying on the ground pale and weak. The town doctor suspects she is suffering from anemia and the next day she passes away.

Megumi is dead and a burial is held for her. Doctor Ozaki is shocked at her sudden death and requests permission to perform an autopsy to determine the exact cause of her death but Megumi's father refuses.

Later two more villagers die suddenly. Growing concerned about so many deaths happen in a short space of time Ozaki contacts the head monk Seishin. Together they discover that ten people have died in the month of August alone. Ozaki fears that the village is in the clutches of an epidemic.

Natsuno investigates local stories of the "Risen" after seeing that someone had disturbed the torn-up pieces of Megumi's letter he threw out. Meanwhile, Masao's brother Hiromi has died of the same mysterious causes, and Masao is bedridden with peculiar bite wounds.

Seishin meets with Dr. Ozaki with his findings, but Dr. Ozaki yells at him over his own frustration with not being to help his patients. Later, Dr. Ozaki notices that most patients with symptoms of the epidemic have "insect bite wounds" on them, and has some success when he performs a blood transfusion on Gyouda Etsuko and she is able to return home. However she later dies after she does not report to the clinic for a follow-up.

Natsuno asks Dr. Ozaki if there was any possibility that Megumi might not have been dead, to which Dr. Ozaki responds jokingly that she would be a zombie or a vampire. This starts Dr. Ozaki thinking that maybe this isn't an epidemic...

Natsuno learns more about the Shiki and warns Kaori and Akira to leave town before it is to late.

Dr. Ozaki tries to tell the townspeople the truth but is laughed off by the villagers believing that he is overworked at the clinic. He then tries to gather evidence to inform the outside world of what is occurring only to find that the Shiki have taken control of the local government and have altered all records so that no one has died in the town on paper. Demoralized and exhausted Dr. Ozaki smokes outside his clinic when Natsuno appears and tells him that he is not alone.

Kaori and Akira find their mother near death. Akira decides to take action and goes to the temple to collect talismans to ward off the Shiki while Kaori prepares stakes. At the same time Tooru is invited to tea with Sunako and learns of her origins as a Shiki.

Natsuno is paid a visit by Tatsumi who informs him that he is one of only four known “werewolf” Shiki, those that can walk in the open sun. That night Tooru is taken to the huts where the Shiki have been putting bodies waiting to see if they turn, inside he finds nurse Ritsuko has turned but has politely refused to drink any blood. At the same time Dr. Ozaki begins his plan to destroy the Shiki by tricking the beautiful but vain Chizuru into coming to the town festival under the pretense of being under her control.

With the village finally believing Dr. Ozaki about the Shiki they begin to plan on how to exterminate them. Sunako hearing about Chizuro’s death orders Tatsumi to prepare the Shiki to finish off the village by killing or turning the bitten on the survivors.

The mountain is on fire and threatens to engulf the entire town. At the same time the final Shiki make their final effort to escape.

In a flashback to right after the events of the first three deaths at Sotoba, a woman named Motoko is shown to be overly protective of her children, going as far as to take them to school everyday. Eventually, as the mysterious deaths start piling up, Motoko's father-in-law dies. Her mother-in-law refuses to let Toshio perform an autopsy on the body, claiming that doctors care about the money more than their patients. Eventually Motoko's husband dies; then, her daughter falls ill. Slowly losing her sanity, Motoko carries her daughter over to the Ozaki clinic; however when she arrives, the clinic is closed (because Toshio is conducting experiments on his risen shiki wife.) She then rushes over to the Kanemasa clinic, which is also closed during the daytime. Motoko's mother-in-law shows up and scolds her for shaming herself in public, and states that her daughter is fine.