| Silvertubes | Western Cape |
| Simodisa Start-Up | Gauteng |
| SimpliFind | |
| Simulation Engineering Technologies (Pty) Ltd | Gauteng |
| Sinetech (Pty) Ltd | Gauteng |
| SITA | Gauteng |
| SiteCreations SA | Gauteng |
| SiteMeUp Online Marketing (Pty) Ltd | Western Cape |
| SitesDeveloper | |
| SiteWorx IT Services | Western Cape |
| SIVOXI | |
| Six Digital | Gauteng |
| Six Sigma South Africa | Western Cape |
| Siyelo | Western Cape |
| Sizwe Africa IT Group | Gauteng |
| SK Telecom (Pty) Ltd | Gauteng |
| Skyrove | Western Cape |
| Skytouch Hosting | |
| Skytouch Media | Western Cape |
| Slyce Online | Gauteng |
| small BITS Software CC | Gauteng |
| SmallBizCRM | Western Cape |
| Smart Digital Media | Western Cape |
| Smart Options | Western Cape |
| Smart Retail | Gauteng |
| Smart SEO | KwaZulu-Natal |
| Smart-IT | Western Cape |
| SmartBlade | |
| SmartVoice | Gauteng |
| Smartweb Group (Pty) Ltd | Western Cape |
| SmartXchange | KwaZulu-Natal |
| Smollan | |
| Smudge | Gauteng |
| SnapBill (Pty) Ltd | Western Cape |
| Snapt | Western Cape |
| So Interactive | Gauteng |
| Soft Edge Solutions | Gauteng |
| Softnet | Free State |
| Softoit | Gauteng |
| SoftPageCMS | Western Cape |
| Softserve | |
| SoftSmart Tech (Pty) Ltd | |
| Software Africa | Gauteng |
| Software Colors (Pty) Ltd | Western Cape |
| Software Control Services (Pty) Ltd | Gauteng |
| Software Farm | Gauteng |
| Software Testing Solutions (Pty) Ltd | Gauteng |
| Sol Plaatje University | Northern Cape |
| SolarWorks | |
| Solid Systems | Western Cape |