Sotobamura is a small village with around 1300 residents; so small the village isn't even connected to a single highway. An isolated village in which old customs, such as the burial of the dead, are still practiced. One day, the bodies of three people are found dead. Although Ozaki Toshio, the village's lone doctor, feels uncertain, he treats the deaths as a normal occurrence. However, in the days following, the villagers start to die one after the other.
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.
Dr. Ozaki is convinced that Nao Yasumori has contracted the same illness that killed Megumi and several other in the village. He conducts numerous tests, all of which return conflicting results that do not match any known disease. Nao dies just like the others from an unknown cause. Meanwhile Natsuno wearily continues his daily life with his best friend Mutou Tooru. The words of his frenemy Murasako Masao, "Megumi might hate you so much she'll come back to visit you!", leave Natsuno shaken. A terrifying thought that the feeling that someone is still watching him just like Megumi did could be real. The monk Seishin is visited by a young girl named Sunako and tells him she really enjoyed his novels.
Dr. Ozaki holds a meeting with the staff at the clinic and announces his belief that an epidemic of unknown origin is present in the town and his killed 19 people. He asks them to be vigilant in looking for people exhibiting the known symptoms but not to tell anyone in fear of starting a mass panic. Natsuno continues to have dreams about Megumi staring at him through his bedroom window. The dreams become so disturbing for him that he has trouble sleeping and ask to spend the night at his friend Tooru's house. That night Natsuno has the most vivid dream yet, that Megumi is now in the room with him.
Seishin talks to the relatives of the recently deceased and discovers the pattern that all of them became ill and weak only a few days before they died and that many quit their jobs before becoming ill. He also learns that many families have suddenly picked up moved in the middle of the night without telling anyone. Tooru dies suddenly, and at the funeral Natsuno and Masao get in an argument that ends with Masao running home crying complaining about how no one appreciates him. Arriving at his home he sees a white figure go around back. Following him he finds nothing, as he opens the backdoor the tree above him rustles with movement.
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...
Masao awakens to find himself lying on a bed of flowers, six feet under. Natsuno joins forces with Kaori and Akira and convinces them to help him dig up Megumi’s grave to confirm if she is really dead or if she has “risen”. Meanwhile after his brief encounter with Natsuno, Dr. Ozaki has become convinced that vampires are responsible for the mysterious death in the village. He decides to keep watch over his latest patient as a test of this new theory.
Natsuno, Kaori and Akira dig up Megumi’s grave to confirm if she has truly risen or not. Finding her coffin empty Kaori is suddenly attack by a strange man whose body is as cold as a corpse. Later unbeknownst to them Natsuno’s parents are visited by a strange girl who asks to be let into the house.
Dr. Ozaki and Seishin vainly try to save an elderly patients life. After a blood transfusion seems to return her strength Dr. Ozaki is sure that he has discovered the cure. That night he is shown irrefutable proof that the plague is actually a vampire plot. Join them or die.
Natsuno house is visited by a strange young girl who demands to be invited in. When Natsuno returns home his parents tell him about the girl but she is gone. Realizing that his parents have given permission to the vampire to enter his house at any time he prepares for them to come for him. Sure that it will be Megumi who comes for him he his shocked to his core when he sees who has come for him.
While Sotoba's villagers are debating the cause of the frequent deaths, the town shaman points her finger at the residents of Kanemasa mansion.
Natsuno learns more about the Shiki and warns Kaori and Akira to leave town before it is to late.
Natsuno may be dead but will he rise? Dr. Ozaki discovers that his wife is already in the final stages of having her blood drained. After she flat lines during the night he tells everyone that he will take care of her, but how does one take care of a dead person?
Kaori's father suddenly collapses. At the clinic, Dr. Ozaki studies his wife's corpse for clues on how to combat the Shiki.
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.
Seishin finds that his bed ridden father has disappeared without a trace. Kaori shows up at the temple covered in dirt her hair and eyes crazed with desperation and begs Seishin to give her last rights so that she will be ready when Megumi comes to kill her like the rest of her family. Dr. Ozaki methodically prepares stakes when nurse Ritsuko calls claiming that one of the other nurses Kiyomi called saying someone had kidnapped her. Dr. Ozaki rushes to stop Ritsuko from leaving the safety of her house.
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.
With the first day drawing to a close the village has killed many Shiki but Dr. Ozaki believes that they haven’t most of them. Tooru is forced to make a decision about Ritsuko refusing to drink blood and as dawn breaks on the 2nd day a new form off attack is revealed by the Shiki.
The villagers finally discover where Sunako is hiding. Tatsumi creates a distraction to lure them away while Seishin tries to carry her to safety.
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.