Isabella Clark (-1857) was the first wife of Sir John A. Macdonald, first Prime Minister of Canada. She was his second-cousin; they had a maternal grandmother in common. She became ill after just two years marriage in 1845 and died of unknown causes after 13 years of misfortunate marriage, set mostly in sickrooms. They had two sons: John and Hugh, the former died at 13 months. She had also developed an addiction to opium mixed with wine.