By 1636 he had returned to England and lived in Clerkenwell, London, during a plague epidemic. He and Henry Morse ministered to the sick in Westminster, and raised money for the families of victims. Southworth was arrested again in November 1637 and sent to the Gatehouse Prison and again transferred to The Clink, where he remained for three years. Four times Southworth was arrested, and three times released by the Secretary of State Sir Francis Windebank at the direction of the Queen. The fourth time he managed to escape. From 1640 and 1654 he continued his clandestine ministry.