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Nathaniel Littleton was born in 1605 in Shropshire, England. His parents were Edward Littleton and Mary Walter. He married Ann Southey, daughter of Henry Southey and widow of Charles Harmar, in about 1640. They had three children, Edward, Southey and Esther. Nathaniel died in 1654 in Northampton County, Virginia. Descendants and relatives lived mainly in Virginia and Maryland.