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Big Sister may refer to:
- Big Sister (software), network monitoring software
- Big Sister (brothel), an online brothel in Prague
- "The Big Sister", an episode of Dexter's Laboratory
- "Big Sister," a song by Elvis Costello and the Attractions from Trust (Elvis Costello album)
- Big Sister's Island, one of the Sisters' Islands of Singapore
- Big Sisters part of the Big Brothers, Big Sisters program.
- Big Sister (radio) was a radio soap opera
- Big Sister, an enemy type in the game BioShock 2.
- Big Sis, a nickname for Secretary of Homeland Security Janet Napolitano
- Stóra systir, an anti-prostitution vigilante group in Iceland
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