| Solumed | Gauteng |
| Solution Technologies | Gauteng |
| Solutioncoms | Gauteng |
| Somco Cape | Western Cape |
| SOS Web Services | KwaZulu-Natal |
| Sound Idea Productions | Gauteng |
| SoundsReal | Western Cape |
| South Africa Perl Mongers | Gauteng |
| South African Business Angel Network | Gauteng |
| South African College of Applied Psychology | |
| South African Mathematical Society | Gauteng |
| South African National Bioinformatics Institute | Western Cape |
| South African National Space Agency | Western Cape |
| South African Oracle User Group | Gauteng |
| South African Reserve Bank | Gauteng |
| SouthBit Data Recovery | Western Cape |
| Southern Africa Venture Capital and Private Equity Association | Gauteng |
| Southern African Analytics (Pty) Ltd | Gauteng |
| Southern African Regional Universities Association | Western Cape |
| Southern Sons Group (Pty) Ltd | Gauteng |
| Southsoft | Gauteng |
| Sozo Labs | Western Cape |
| Space Television | Gauteng |
| Spaceacre | Western Cape |
| Spartan Technology Rentals (Pty) Ltd | Gauteng |
| Speak Geek | Gauteng |
| Spectrum Concepts | Gauteng |
| Spectrum Security Products | Western Cape |
| SpeedSurf | KwaZulu-Natal |
| Spider Web Hosting | |
| Sporatec | |
| Springlab (Pty) Ltd | Western Cape |
| Spyderweb Design | Western Cape |
| Square Plan | Gauteng |
| Sromix | Gauteng |
| Stallion Hosting | KwaZulu-Natal |
| Standard Bank | Gauteng |
| Starbright | Gauteng |
| Starsun Import Export | Gauteng |
| StartUp 90 | |
| StartUp 90 Accelerator | Western Cape |
| Steinie's Web Designs | Gauteng |
| Stellenbosch Business School | |
| Stellenbosch University - Applied Mathematics | Western Cape |
| Stellenbosch University - Computer Science | Western Cape |
| Stellenbosch University LaunchLab | Western Cape |
| Stellenbosh University | |
| Stem Connect | |
| Stempath Laboratories | |
| Stitch | |