The game takes place during the 17th century, 17 years after the events of Soul Calibur 4, with Nightmare's death by the hands of Siegfried. The main protagonist is Patroklos and the deuteragonist is Pyrrha, son and daughter of Sophitia and Rothion Alexander and nephew and niece of Cassandra Alexandra.

Although no official storyline for the game has been released so far, Patroklos' storyline says that Pyrrha and Patroklos haven't had an easy childhood as their mother, Sophitia, was killed by a "malfested" and their father died an untimely death from a disease. Pyrrha was abducted at a young age and remembers nothing of her childhood, including her family ties. Her brother Patroklos, on the other hand, was raised by his father and is now searching his older sister. He also searches and destroys the malfested.

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