Despain, DeSpain, or D'Spain is a surname. Notable people with the surname include:
Bree Despain (born 1979), American author Dave Despain (born 1946), American motorsport journalist Don G. Despain (1940–2022), American botanist, plant ecologist, and fire behavior specialist Emira D'Spain (born 1996), American model, influencer, and television personality Michelle Despain (born 1984), Argentine-American luger Pleasant DeSpain (born 1943), American author
See also Despaigne Spain (surname)