S81 may refer to :
- S81 postcode for the Bassetlaw, Rotherham area
- S81 (New York City bus) serving Staten Island
- BenQ-Siemens S81, a BenQ-Siemens mobile phone
- Blériot-SPAD S.81, a 1923 French fighter aircraft
- County Route S81, a county route in Bergen County, New Jersey
- Indian Creek, Idaho's USFS airport FAA LID
- Isaac Peral (S-81), a Spanish submarine under construction
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