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His father Friedrich Wilhelm Leyser (1622–1691) was the son of Polykarp Leyser II and grandson of Polykarp Leyser the Elder, both also theologians. His mother was Friedrich's wife Christine Margarethe Malsius (c 1630–before 1720).
He married Margaretha Magdalena Barckhausen (1666–1699), daughter of the theologian Hermann Barckhausen (1629–1695) and his wife Magdalena Gesenius († 1677). They had two children, including the theologian, philosopher and historian Polykarp Leyser IV (1690–1728). He later remarried, having two more children with his second wife.