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Lowell married his first wife, Sarah (January 14, 1745 – May 5, 1772), sister of Stephen Higginson, on January 8, 1767.^{[citation needed]} They had three children, including John Lowell Jr. (1769–1840). John Lowell Jr.'s descendants include businessmen John Amory Lowell, Augustus Lowell, and Ralph Lowell; federal judges John Lowell and James Arnold Lowell; and siblings author and innovator Percival Lowell, Harvard President A. Lawrence Lowell, and poet Amy Lowell.^{[citation needed]} Lowell's wife Sarah died on May 5, 1772.^{[citation needed]}

From his practice of the law and shipping ventures John was able to acquire a large estate and a considerable sum of money throughout his lifetime and despite not being from the richest family growing up he was able to raise the value of the Lowell name.