Sisco could refer to:

• Kristina Sisco, an American actress
• Karen Sisco, a fictional United States Marshal created by novelist Elmore Leonard, or the TV series of the same name. She also appears in the film Out of Sight
• Sisco, Haute-Corse, a commune on Corsica, France

Sisko could refer to the following fictional characters from the television series, Star Trek: Deep Space Nine:

• Benjamin Sisko
• Jake Sisko
• Jennifer Sisko
• Joseph Sisko

Sisko may also refer to Sisqó, an R&B performer and the lead singer of Dru Hill

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