| Acronym | Meaning |
 | SBIR | Small Business Innovation Research |
| SCA | Shuttle Carrier Aircraft |
| SCT | Schmidt-Cassegrain Telescope |
| SDI | Strategic Defense Initiative |
| SDIO | Strategic Defense Initiative Organization |
| SDSS | Sloan Digital Sky Survey |
| SECO | Sustainer Engine Cutoff |
| SEDS | Students For The Exploration And Development Of Space |
| SEI | Space Exploration Initiative |
| SEM | Space Environment Monitor |
| SEP | Societe Europeenne De Propulsion |
| SEPAC | Space Experiments With Particle Accelerators |
| SEST | Swedish ESO Submillimeter Telescope |
| SETI | Search For ExtraTerrestrial Intelligence |
| SHARE | Space Station Heat Pipe Advanced Radiator Element |
| SID | Sudden Ionospheric Disturbance |
| SIR | Shuttle Imaging Radar |
| SIRTF | Space InfraRed Telescope Facility |
| SIXA | Silicon X-ray Array |
| SL | (Comet) Shoemaker-Levy / SpaceLab |
| SL-J | SpaceLab Japan |
| SLAP | Space Link Access Protocol |
| SLAR | Side-Looking Airborne Radar |
| SLC | Space Launch Complex |
| SLF | Shuttle Landing Facility |
| SLS | Space(lab) Life Sciences |
| SMC | Small Magellanic Cloud |
| SME | Solar Mesosphere Explorer |
| SMEX | Small EXplorers |
| SMM | Solar Maximum Mission |
| SMS | Shuttle Mission Simulator |
| SN | SuperNova |
| SNG | Sodruzhestva Nezabisimikh Gosudarst |
| SNR | Signal To Noise Ratio / SuperNova Remnant |
| SNU | Solar Neutrino Units |
| SOB | Strap-On Booster |
| SOCC | Satellite Operations Control Center |
| SOFI | Spray-on Foam Insulation |
| SOFIA | Stratospheric Observatory For Infrared Astronomy |
| SOHO | SOlar Heliospheric Observatory |
| SOLSTICE | Solar Stellar Irradiance Comparison Experiment |
| SPAN | Space Physics And Analysis Network |
| SPARTAN | Shuttle Pointed Autonomous Research Tool For Astronomy |
| SPAS | Space Pallet Satellite |
| SPDM | Special Purpose Dextrous Manipulator |
| SPH | Smoothed-Particle Hydrodynamics |
| SPOT | Systeme Probatoire Pour L'Observation De La Terre |
| SPS | Solar Power Satellite |
| SPTN | SPARTAN |
| SR | Special Relativity |
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