Sanguinaire overhauls the vanilla lycanthropy gameplay to deliver a far more creative experience than the one in the base game. In Sanguinaire, as a werewolf, the player will not simply gain a transformation power, and joining the companions is not the only way the player can achieve Lycanthropy.

Disease: The player can contract Sanies Lupinus from other warewolves in the game if they are not already a werewolf themselves. If the disease is not cured, the player will succumb to the change after 3 days of inclubation.

Primary changes to Lycanthropy: Similar to older Elder Scrolls Games, the player will no longer have the power to shift when they desire it as a standard werewolf. Instead, they will forcefully shift at night between 9pm and 3am. While in werewolf form, the player must feed on a least one humanoid before they return to their normal state of being to avoid a nasty health debuff, which they must live with until their next opportunity to shift. The player will benefit from a variety of passive perks while in humanoid form, as they progress their Lycanthropy skill which is achieved through feeding in wolf form.

On becoming a werewolf, the player will as in the vanilla game gain a resistance to disease. In addition, they will gain a 50% resistance to normal weapons, and bestial strength (which will increase in potency as their werewolf skill increases).

Werewolf Skill Progression: The player will slowly increase their Werewolf skill as they feed on the corpses of their prey. Eventually this will make the player more powerful in humanoid form, something that was implied in the vanilla game but never actually implemented.

Werewolf Skill Level 1: Bestial Strength; Unarmed and Melee strikes deal 10 additional damage.
Werewolf Skill Level 2: Bestial Strength; Unarmed and Melee strikes deal 15 additional damage, Unlocks Persuit: Stamina increased by 50 points.
Werewolf Skill Level 3: Bestial Strength; Unarmed and Melee strikes deal 20 additional damage, Unlocks Blood Rage: Increases power attack damage by 20%.
Werewolf Skill Level 4: Bestial Strength; Unarmed and Melee strikes deal 25 additional damage, Unlocks Call of the Pack: Wild wolves do not attack you.
Werewolf Skill Level 5: Bestial Strength; Unarmed and Melee strikes deal 30 additional damage
Werewolf Skill Level 6: Bestial Strength; Unarmed and Melee strikes deal 35 additional damage

The Ring of Hircine: Indicated in the original game dialogue but never implemented by Bethesda, the Ring of Hircine will now grant the ability to turn when desired, and suppress the forced transformations at night. The blessing of Hircine essentially gives the player more control over their condition, and a way to escape the curse's more detrimental effects.

Werewolf and Vampire Hybridism: There is a daedric artifact hidden within the game that will allow a werewolf to become a vampire / werewolf hybrid under the right conditions. If the player has this item, and visit's Lord Harkon to become a vampire lord while wearing the ring, they will become a Hybrid. Harkon has custom dialologue for this revelation, which is fully voiced.