| Acronym | Meaning |
 | SIMAS | Shuttle Information Management Accountability |
| SIMAS | System |
| SIMCOM | SimulationComplex |
| SIMFAC | Simulation Facility |
| SIMO | Simultaneously |
| SIMR | Systems Integration Management Review |
| SIMS | Shuttle Imaging Microwave System |
| SIMS | Shuttle Inventory Management System |
| SIMU | Simulated Inertial Measurement Unit |
| SIN | Sine |
| SIO | Serial Input/output |
| SIO | Systems Integration Office |
| SIP | Scientific Instrument Package |
| SIP | Separation Instrument Package |
| SIP | Strain Isolation Pad |
| SIP | Strain Isolator Pad |
| SIP | SYstems Integration Office |
| SIPS | Small Instrument Pointing System |
| SIR | Shuttle Imaging Radar |
| SIR | Software Initiated Restart |
| SIR | System Interface Requirements |
| SIR | Systems Integration Review |
| SIR-A | Shuttle Imaging Radar@A |
| SIRR | Software Integration Readiness Review |
| SIS | SAIL Interface System |
| SIS | Scanning Imaging Spectrometer |
| SIS | Serial Input Special |
| SIS | Shuttle Information System |
| SIS | Shuttle Interface Simulator |
| SIS | SiMUlator Interface SYstem (SubsYstem) |
| SIS | Software Implementation Specification |
| SIS | Software Integrated Schedule |
| SIS | Standard Interface Specification |
| SIS | Systems Integration Schedule |
| SISWG | STS Integrated Schedule Working Group |
| SIT | Shuttle Integrated Test |
| SIT | Shuttle Interface Test |
| SIT | Situation |
| SIT | Software Integrated Test |
| SIT | SSV Integrated Test |
| SIU | Signal Interface Unit |
| SIU | Signal Interface Unit |
| SIV | Sieve |
| SIVE | Shuttle Interface Verification EquiPment |
| SKD | Singer |
| SL | Sea Level |
| SL | Seal |
| SL | Shelf Life |
| SL | Sound Level |
| SL | SPacelab |
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