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Bloodstained takes place in 18th century England during the Industrial Revolution. Fearing the loss of their influence over their wealthy patrons, the Alchemy Guild researched methods to summon demons and created Shardbinders, humans forcibly fused with demonically charged crystals that attuned them to their powers. These Shardbinders were sacrificed by the Guild to summon demons from Hell in what was meant to be a scare tactic but instead brought uncontrollable destruction that wiped out the Guild and much of England until the Church was able to banish them. Of the sacrificed Shardbinders, only one named Gebel survived. Another Shardbinder, the main protagonist Miriam, is spared due to falling into an unnatural slumber before she can be sacrificed.[1]

Ten years later in the game's present-day, Miriam has awakened from her slumber and has learned that Gebel has summoned the demons to destroy England as he seeks revenge on the surviving alchemists for what they did to him.[2] Accompanied by Johannes, a former member of the Alchemy Guild, they sail across the ocean to Arvantville, a destroyed village on the outskirts of Gebel's castle, the Hellhold. They meet with Johannes's friend Dominique, an exorcist who helped Johannes care for Miriam during her slumber and has been sent by the Church to help them stop Gebel.[3]

As Miriam begins her journey into the Hellhold, she confronts Alfred, a surviving member of the Alchemy Guild and the former mentor to Johannes. Alfred seeks to recover an ancient book used in the demon summoning by Gebel, the Liber Logaeth, and threatens to kill Miriam if she does not leave. As his former student, Johannes deeply distrusts Alfred's motives and fears he may be making another mistake, partially feeling responsible for the actions that Alfred and the other alchemists took in harming Gebel, Miriam, and the other Shardbinders.[4] She also crosses paths multiple times with Zangetsu, a demon hunter from Japan who initially distrusts Miriam due to her Shardbinder powers having ties to demons, but over time begins to respect her strength. Zangetsu explains that he is seeking a demon named Gremory, who is continuously eluding him for fear of his power. He gives Miriam his katana thinking that Gremory will not expect her to be wielding it and drop her guard.