| SIGA (Electronics) Ltd | Bedfordshire |
| Sigma Capital Group Ltd | |
| Sigma Games Ltd | |
| Sigma Messaging | |
| Sigma Polaris Ltd | |
| SIGMA Technology Solutions Ltd | |
| Sigma Web Ltd | Wrexham County Borough |
| SigmaOS Software Ltd | |
| Sign In App Ltd | |
| Sign-Up Technologies Ltd | Surrey |
| Signable | |
| Signal AI | |
| Signal Media Ltd | |
| Signal Networks Ltd | Bristol |
| Signalator Ltd | |
| Signaloid | |
| Signapse Ltd | |
| Signatur Biosciences | |
| Signature AI Ltd | |
| SigniFlow | |
| SignTech Paperless Solutions | |
| Signum Solutions | |
| SignUpAnywhere | |
| Sikoia Ltd | |
| Silchester Control Systems | Hampshire |
| Silence Therapeutics | |
| Silent Games | |
| Silico | |
| Silicon Alley | Essex |
| Silicon Beach Training | |
| Silicon Corridor Linux User Group | Berkshire |
| Silicon Dales Ltd | Greater Manchester |
| Silicon Infusion Ltd | Hertfordshire |
| Silicon Microgravity | |
| Silicon Reef | |
| Silicon Roundabout Ventures | |
| Silicon Technix | |
| Siliconexion | Leicestershire |
| Silkmoth | Cheshire |
| Silkstream Ltd | Essex |
| Silobreaker Ltd | |
| Silver Softworks | |
| Silver Telecom Ltd | Newport |
| Silver Touch Technologies Ltd | |
| silverAds | |
| SilverArrow Capital Holding Ltd | |
| Silveray | |
| Silverchip | Greater Manchester |
| Silverink | Ards and North Down |
| Silverlink PCS Software Ltd | |