When a series of "vampire" murders sweeps the city, Toronto Police detective Nick Knight is put on the case. However, unknown to everyone except medical examiner Natalie Lambert, Nick is also a vampire trying to regain his own mortality. When the next victim is a guard at the Natural History Museum, Nick and Detective Schanke discover that a Mayan ceremonial goblet was also taken, one which curator Alyce Hunter notes was used to drink the blood of sacrifice victims. Forced to retreat to his loft apartment during the day, Nick darkens the room and drinks animal blood from a goblet identical to the one stolen from the museum while anxiously waiting for Natalie to find a cure. When Alyce comes across a century-old photograph of an archaeologist who looks exactly like Nick, she discovers the cup was one of a pair that, together, are thought to cure vampirism. Though attracted by the museum curator, Nick is forced to resist his impulse to drink her blood and returns home shaken by how easily he could have killed Alyce. Told that he must stop drinking blood for a cure to work, Nick insists that it is too difficult to change, but Natalie threatens to stop her treatments if he doesn't cooperate. Meanwhile, when a homeless couple disappears from his neighborhood, Nick worries that they are the latest victims of the vampire killer. After telling Natalie about Lacroix, the vampire who brought him over to the netherworld centuries ago, Nick reveals that his master would do anything to keep him from recovering his mortality. Suspecting Lacroix of being behind the killings and the theft of the goblet, Nick learns of the murder of his homeless friend, Topper, but wonders what has become of his companion, Jeanie. Turning to Janette, another vampire from 13th Century France, Nick is told of Lacroix's whereabouts and plunges headlong toward a confrontation, unaware he is being followed by Alyce.

Arriving at the warehouse Lacroix is using as a radio station, Nick is unaware of being followed by Alyce as he prepares to confront his vampire master. As Alyce watches Lacroix taunt Nick with the Mayan goblet that could spare him his tortured life, she accidentally reveals her presence and is stopped while trying to escape. Torn between saving the life of a woman that he thinks he could love and the goblet that could restore his humanity, Nick chooses to rescue Alyce, watching helplessly as the cup crashes to the floor below. Racing for his car to avoid burning up in the morning sun, Nick locks himself in the trunk to remain until darkness falls again. However, finding his partner's car, Schanke decides to use it for the day, unaware he is sleeping in the trunk. Although Schanke is unable to get any information, making his way from the car to a hospital office, Nick tells Natalie that Lacroix is not responsible for the killings, confirming his partner's hypothesis that the victims are being chosen because they are homeless donors at a mobile blood bank. Meanwhile, Jack Fenner, the blood mobile's technician, disables Nick's car, nearly killing Schanke in order to mask his responsibility for the killings. Alyce breaks into Nick's apartment and finds the matching jade cup, but when a badly beaten Jeanie arrives, she calls for an ambulance to help the homeless woman. When Fenner arrives looking for Jeanie, Alyce mistakes him for a paramedic and lets him into the loft. However, after he calls home and hears Fenner trying to kill them, Nick hurries to save the women. As fire consumes the loft, Jeanie is led outside to safety, while Nick and Alyce watch Lacroix feasting on the blood of the dying Fenner. Weakened from a lack of nourishment and taunted by Lacroix, Nick offered Alyce's blood as a sacrifice. Though Lacroix encourages him to drink, Nick musters all of his strength to resist the temptation and attacks his master through the wall of flames. However, when Lacroix takes her for himself, Nick kills the vampire with a fiery stake through his heart, but also loses Alyce in the process. Finally, returning to Natalie, Nick is revived with a blood transfusion to continue his struggle to become a mortal.

During his investigation of a series of ritual murders whose victims are all from the same church, Nick is forced to face his fear of the religion and its symbols in order to pursue the case, while reviving painful memories of his encounter with Joan of Arc in France centuries ago. Meanwhile, after the killer confesses, and torn over whether to reveal his information, Father Pierre Rochefort abides by the sanctity of the confessional and keeps silent, choosing instead to stop the killer himself. Despite warnings from Nick to stay away, Schanke goes to Janette's eerie nightclub, where he is saved at the last minute when the owner interrupts an attempt to make him a vampire's victim. While suspecting that Father Rochefort knows more about the killings than he will admit to, Nick's acute sense of hearing enables him to interrupt the next attack, where he discovers the priest in an adjacent alleyway. Father Rochefort continues his refusal to tell what he knows of the killer's identity, claiming his belief is the most important thing to him. Although Magda, the woman whose life was saved, offers to help Nick set a trap for the killer, she and Father Rochefort are told to stay away from the church until he is arrested, while Nick forces himself to enter the cathedral during the day, knowing it will be impossible to leave until nightfall. Posing as a priest, Nick waits in the church's confessional, while Magda escapes her police escort and is spotted by the killer. When Schanke sees Magda entering the cathedral, he starts to follow, but is hit from behind by the killer. Told by the half-conscious Schanke about her being at the church, Nick rushes out into the night and swoops down to save Magda from being burned at the stake by forcing himself through a deadly wall of flames. Finally, with the experience giving him a faith he has never known, Nick renews his effort to overcome his vampirism.

A young woman dies, and all evidence points to suicide. Nick has a gut feeling that it was murder but is unable to prove it. Adding to his stack of unsolved crimes, it makes Nick question his own feelings of self-worth, especially after hearing about another, real suicide: that of one of his "old friends". Nick must search through his memories of their relationship of centuries past to determine why she killed herself, and why he shouldn't.

When the wife and daughter of noted charity leader Conrad Hedges are kidnapped, Nick and Schanke are assigned to work with a psychic to uncover evidence leading to the women. Despite Schanke's skepticism, Denise Ford quickly locates the dead body of their chauffeur hidden in a warehouse where the Hedges' limousine was found. But, with her psychic visions clouded by disturbing images of Nick, Denise begins to doubt her own abilities. When Hedges receives a ransom note demanding one million dollars for the return of his family, Nick and Denise are sent to search the family's mansion for clues. After detecting a recent argument between Conrad Hedges and his daughter, Gennifer, Denise bolts from the girl's room when she sees Nick as a vampire. Aware that his presence is clouding Denise's powers, Nick remembers a 17th century Puritan who was similarly disturbed by him. Meanwhile, learning that Schanke has found Mrs. Hedges' body, Nick begins to wonder if a kidnapping actually took place at all. Questioning her own sanity because of her visions of Nick, Denise insists on dropping the case but, when Hedges' disappears with the ransom money, Nick is convinced to tell the psychic the truth about himself in order to bring her back onto the case. With the knowledge of Nick's past clearing her mind of the disturbing visions, Denise returns to the mansion and senses that the two women knew something Hedges wanted kept secret. Based on Natalie's examination of the corpse, Denise follows Nick to a warehouse where they find Hedges with the kidnappers and Gennifer. Admitting responsibility for arranging the abduction to cover up a long history of theft from his charity, Hedges grabs Denise as he attempts an escape. However, Denise is shot during a struggle and, though Nick flies her in his arms to the hospital, he is too late to save her life.

When his surveillance of pornographer and murder suspect Murray Kozak goes sour, Nick is too late to save informant Pete Farber from being shot to death. Though not finding the sought-after videotape of Kozak killing pom actress Betty Gilroy, in order to detain Kozak, Nick falsely claims to having seen him fire the shot that killed Farber. However, after Natalie points out a glaring inconsistency between his story and her autopsy, Nick recalls another disturbing incident where he witnessed Janette kill a female musician and then left her boyfriend to be accused of the murder. When Nick asks to be released from having to testify in person, Stonetree refuses the request, claiming he is the only eyewitness to the murder. Meanwhile, after interviewing a woman well -acquainted with Kozak, Nick concludes that a dancer, Tamara, may know more than she is willing to admit about the deaths of Betty and Farber. Admitting to Schanke that he lied about seeing Kozak actually kill their informant, Nick is told to stick with his original story in order to get the killer off the street. So, with Natalie helping him with the rare daytime appearance, Nick shows up for Kozak's trial, preoccupied by his memory of an 1828 court appearance. After Kozak claims that Pete killed himself, Nick is called to the stand to testify but is unable to bring himself to lie under oath. Rushing from the courtroom to see Janette, Nick is urged to join her to start their lives again in another city, away from the mortal concerns that are troubling him. However, refusing to abandon his desire to become human again, Nick finally admits to having lolled Lacroix. Ostracized by his fellow officers for allowing Kozak to go free, and by Janette for killing their mentor, Nick obtains a warrant to search Tamara's home. After arriving in time to overhear Kozak admit to killing both Farber and Betty on Tamara's orders, Nick bursts into the room and arrests the pair for the murders.