Fed up with the lack of bloodthirst from his captives, Monokuma has infected them with the Despair Disease, which manifests as cowardice in the mighty Owari... gullibility in the worldly Mioda... and dishonesty in the, er... in Komaeda.
Afraid that they could commit murder while not in their right mind, the sick students are quarantined, keeping in touch with the 'healthy' students by video monitor... only to find that despite all their precautions, the killing hasn't stopped!