Sepe is an Italian surname. Notable people with the surname include:
Angelo Sepe, (1941–1984) Italian-American gangster Crescenzio Sepe (born 1943), Italian cardinal Daniele Sepe (born 1960), Italian musician Frank Sepe (born 1971), American fitness author Luigi Sepe (born 1991), Italian footballer Majda Sepe, (1937–2006) Slovenian singer Michele Sepe (born 1986), Italian rugby player Mimmo Sepe (1955–2020), Italian comedian