| Scott Bricklaying & Building Limited | Construction | 2016 |
| Scott Fyfe Decorators Limited | Construction | 2022 |
| Scott Keith Limited | Real estate | 1981 |
| Scottroads Ltd | Administrative & support | 2025 |
| Screaming Chimp Chilli Sauce Ltd | Manufacturing | 2016 |
| Screaton and Associates Ltd | Professional & scientific | 2015 |
| Scudd Properties Ltd | Real estate | 2025 |
| Sculpted Stones Co. Limited | Manufacturing | 2025 |
| SD Polishing Ltd | Other services | 2024 |
| Sdaccess Ltd | Administrative & support | 2026 |
| SDK Civils Limited | Construction | 2024 |
| SDK Construction Management Limited | Professional & scientific | 2025 |
| SDR Joinery Limited | Construction | 2023 |
| Sea Way Footwear International Limited | Wholesale & retail | 2010 |
| Sea Wolf Security Services Ltd | Administrative & support | 2025 |
| Seaglass Cafe Ltd | Hospitality | 2023 |
| Seaham Harbour Dock Company | Transport & logistics | 1981 |
| Sealprufe Limited | Construction | 1994 |
| Sean Brennan Electrical Limited | Construction | 2021 |
| Second to None Care Limited | Health & social care | 2018 |
| Sedg (Caergeiliog) Limited | Construction | 2017 |
| Seeshell Grooming Ltd | Other services | 2019 |
| Segnatech Limited | Information & communication | 2024 |
| Select Consulting & Admin Services Ltd | Professional & scientific | 2008 |
| Select Trade Ltd | Wholesale & retail | 2026 |
| Sellaris Ltd | Wholesale & retail | 2025 |
| Selva Psychology Ltd | Health & social care | 2022 |
| Selva Systems Ltd | Construction | 2020 |
| Senlo Construction Ltd | Construction | 2022 |
| Sense Foods Limited | Wholesale & retail | 2019 |
| Sensedurham Ltd | Hospitality | 2017 |
| Sensory Worx Ltd | Health & social care | 2023 |
| Seravia Ltd | Wholesale & retail | 2025 |
| Servegreen Limited | Wholesale & retail | 1994 |
| Service Direct Newco Limited | Public administration | 2006 |
| Serviced Software Limited | Information & communication | 2001 |
| SET UP and Beyond Ltd | Professional & scientific | 2020 |
| Sevennsix Limited | Information & communication | 2023 |
| Seventeen Seven Deli Ltd | Hospitality | 2019 |
| Sevgie Ltd | Wholesale & retail | 2025 |
| Sewart Limited | Professional & scientific | 2012 |
| Sewell & Sewell Ltd | Professional & scientific | 2018 |
| Sewer Services Ltd | Water & waste | 2025 |
| SF Interim Management Limited | Professional & scientific | 2017 |
| SFA Consult Limited | Professional & scientific | 2016 |
| SFC PUB Management Limited | Hospitality | 2026 |
| SG Personnel Ltd | Administrative & support | 2013 |
| Shadows at the Door Ltd | Information & communication | 2026 |
| Shagcan Group Ltd | Wholesale & retail | 2025 |
| Shalom North East Limited | Real estate | 2025 |
| Shalommotorcars Limited | Wholesale & retail | 2025 |
| Shambhalasacred Ltd | Wholesale & retail | 2026 |
| Shape Accountants Limited | Professional & scientific | 2019 |
| Shape Studios Durham Limited | Arts & recreation | 2023 |
| Shape Studios Newcastle Limited | Arts & recreation | 2024 |
| Shaping Futures Wellness Ltd | Arts & recreation | 2019 |
| Shard Windows and Doors Ltd | Construction | 2025 |
| Sharedgrid Ltd | Information & communication | 2025 |
| Shark Construction (NE) Limited | Construction | 2021 |
| Shas Majestic Homes Ltd | Real estate | 2019 |
| Shaun James Holdings Ltd | Financial services | 2021 |
| Shaun Wall Construction Ltd | Construction | 2016 |
| Shaun Wall Property Services Ltd | Real estate | 2025 |
| Shaw & Storr Hospitality Limited | Hospitality | 2025 |
| SHC and Sons UK Ltd | Construction | 2015 |
| SHE Beauty Clinics Limited | Other services | 2020 |
| Shear One Developments Limited | Real estate | 2025 |
| Shear One Investments Ltd | Financial services | 2024 |
| Sheltered Social Housing Limited | Real estate | 2024 |
| Shepherds of Durham Limited | Hospitality | 1979 |
| Sheraton Bloodstock Limited | Agriculture & fishing | 2018 |
| Sheraton Park Management Limited | Real estate | 2003 |
| Sherburn Carwash & Valeting Ltd | Administrative & support | 2021 |
| Sherburn Taxis Limited | Transport & logistics | 2018 |
| Shield Security Consulting Ltd | Administrative & support | 2025 |
| SHIFT6 Media Intelligence Ltd | Professional & scientific | 2023 |
| SHIFT6 Studios Ltd | Professional & scientific | 2016 |
| Shifting OUR Minds CIC | Health & social care | 2021 |
| Shincliffe Polymers Limited | Wholesale & retail | 2021 |
| Shincliffe Property Limited | Real estate | 2025 |
| Shine Reach & Wash Cleaning Services Ltd | Administrative & support | 2019 |
| Shining Stars Parkhill Ltd | Education | 2021 |
| SHO Global Ltd | Wholesale & retail | 2025 |
| Shoal Media UK Ltd | Information & communication | 2017 |
| Shoesize Records Ltd | Information & communication | 2017 |
| Shoplite BZ Ltd | Wholesale & retail | 2025 |
| Shortcuts Durham Ltd | Wholesale & retail | 2024 |
| Shotton Indian Takeaway Ltd | Hospitality | 2025 |
| Shotton Part Exchange Centre Ltd | Wholesale & retail | 2014 |
| Shotton Tandoori Takeaway Ltd | Hospitality | 2024 |
| Shout Loud Social Limited | Professional & scientific | 2023 |
| Showman Direct Limited | Financial services | 2025 |
| Shroud Ltd | Wholesale & retail | 2023 |
| Shumbanhete Limited | Other services | 2015 |
| Shutterbug Focus Photography Ltd | Professional & scientific | 2025 |
| Shyllot Consulting Limited | Administrative & support | 2021 |
| Siddle Hospitality Ltd | Hospitality | 2022 |
| Sidgwick Clough Peile Ltd | Wholesale & retail | 2025 |
| Sigma Injection Ltd | Manufacturing | 2014 |
| Sigma Subsea Limited | Professional & scientific | 2023 |