Hepburn married in 1511 (the first of her four husbands) Agnes (died February 1557), the illegitimate daughter of James Stewart, 1st Earl of Buchan by Margaret Murray. This Agnes Stewart was provided with Letters of Legitimacy, confirmed by Queen Mary of Guise, on 31 October 1552, under the Great Seal of Scotland. Hepburn and Agnes had one child: Patrick. Hepburn was killed at the Battle of Flodden, where he commanded the Scottish reserve.