Werewolf Venom is an ability of werewolves and vampire-werewolf hybrids to generate an extremely deadly toxin that is fatal to vampires and harmful to Original Vampires. It is secreted through their fangs which allow them to be transferred through a bite.
They are produced by the salivary glands found in mouths of both werewolves and hybrids and is usually used as a weapon against their vampire enemies, as one of the easiest methods of killing a vampire.
To hybrids, it is activated at will either in human form or in werewolf form due to their ability to fully control their transformations at will.
To beasts, it is activated with their 'true face' as they are upgraded vampires.
Whenever a vampire is bitten by a werewolf or hybrid, the venom will be transmitted into the vampire's bloodstream from the werewolf's mouth. Once the blood is contaminated by the toxin, the vampire's heart will pump the venom throughout their entire cardiovascular and systemic circulatory system, during which time it will infect every cell in the vampire's body.
The length of time needed for the saliva to destroy the bitten vampire can vary based on several factors, such as whether it was a werewolf or hybrid who bit the vampire and how transformed the werewolf was at the time. After bitten by a very experienced and fully-transformed werewolf named Jules, the vampire Rose-Marie rapidly deteriorated until Damon Salvatore ultimately decided to euthanize her roughly a day afterward. On the other hand, when Damon himself was bitten by Tyler Lockwood, a new werewolf on his second full moon who wasn't fully transformed at the time (he was still fully-clothed in human form, with only his eyes and fangs having transformed), it took approximately three days for him to be on the verge of death.
A werewolf’s bite will also cause a vampire to hallucinate and go rabid as if it were a wild animal, causing them to lash out as their bodies went into survival mode in hopes that human blood would heal them. A vampire's death by a werewolf bite is very slow and painful, which is why many who are bitten are ultimately "mercy-killed" before they reach that point. Werewolf bites cannot kill an Original Vampire, as Elijah Mikaelson mentioned to Elena Gilbert when they were talking about how to kill Klaus Mikaelson. However, it does weaken them temporarily, as Rebekah Mikaelson felt dizzy and had severe hallucinations after drinking a beer laced with a concentrated dose of hybrid venom. It wore off within hours; she just had to rest for a while for her body to metabolize it.
In The Rager, it was shown that one can extract werewolf/hybrid venom by using a syringe inserted into the werewolf in question's gums to take a sample. From there, it can be used mixed in food or drink (such as when Connor Jordan injected it into a keg of beer that was delivered to Rebekah's party) or can be used to fill or coat bullets (such as when Galen Vaughn used werewolf venom-laced bullets to shoot Damon in Graduation), and it will affect any vampire who ingests it or is otherwise infected with it. Unlike werewolf bites, hybrid bites are fatal to vampires much more quickly- typically a vampire will die or be on the verge of death within twenty-four hours, as seen in the case of Nadia Petrova.
However, Dr. Wes Maxfield thought it possible to synthesize a cure from the venom of a werewolf and the speculation was revealed to be correct as Kingmaker Land Development Inc. created a vaccine that can cure the venom. An indirect cure was found in the antidote to the Ripper Compound which cured Elena of being an Augustine Vampire along with the toxin infused with her at the time.
The Venom of The Beast has no known cure, though based on a Siphoner's ability to siphon 'magic', this is likely the only known loophole.
There is no permanent cure for the venom produced by Upgraded Original Vampires, but Klaus' blood can alleviate its symptoms.
It has not been shown how a werewolf bite would affect a human in the case that they are attacked (which is unlikely due to their ferocity and above-vampire prowess). When the supernatural vampire hunter Connor laced the keg of beer at Rebekah's party with werewolf venom, quite a few humans drank it with seemingly no consequences, so it can be presumed that werewolf venom itself has no effect on typical human beings. Klaus fed on the human Camille O'Connell in Après Moi, Le Déluge and she felt fine afterwards.
- Damon, Elena and Rebekah are the only main vampires who have suffered the effects of werewolf venom without actually being bitten by a werewolf or hybrid (Though Damon had also been bitten by a werewolf prior to that experience).
- There are seven known strains of werewolf venom stemming from each of the seven original werewolf bloodlines.
- Damon mercy-killed Rose and Will before the effects of the werewolf bite could be fatal.
- Nadia Petrova, Finn Mikaelson and Camille O'Connell are the only vampires shown on screen to die solely due to a werewolf/hybrid bite so far.
- It was speculated by Wes Maxfield that because werewolf venom is a toxin, it could presumably have an antidote created by scientific means rather than Klaus' blood. However this was never proven only mere speculation.
- Mikael, like the rest of the Original vampires, cannot be killed by werewolf bites. However, he demonstrated in Live and Let Die that because of his indomitable will and warrior instincts, he is capable of fighting through the effects of the werewolf venom with great focus. As a result of this ability, he was able to recover from the bites much faster than his children Elijah and Rebekah did when they were infected with the venom. In From a Cradle to a Grave, Mikael drank the blood of vampires who had been bitten by numerous werewolves with little to no negative effects, as well.
- This was proven untrue, as the venom of The Beast(a mix of the venom of the seven royal bloodlines), can kill them.
- A Siphoner is able to siphon the magic from the bite.
- In Behind the Black Horizon, Finn became the first Original vampire to die from werewolf venom.