Traditional treatments for bone repair with allografts and autografts are limited by the source of bone substitutes. Bone tissue engineering via a cell-based bone tissue scaffold is a new strategy for treatment against large bone defects with many advantages, such as the accessibility of biomaterials, good biocompatibility and osteoconductivity; however, the inflammatory immune response is still an issue that impacts osteogenesis. Sphingosine 1-phosphate (S1P) is a cell-derived sphingolipid that can mediate cell proliferation, immunoregulation and bone regeneration. We hypothesised that coating S1P on a β-Tricalcium phosphate (β-TCP) scaffold could regulate the immune response and increase osteogenesis. We tested the immunoregulation capability on macrophages and the osteogenic capability on rat bone marrow stromal cells of the coated scaffolds, which showed good biocompatibility. Additionally, the coated scaffolds exhibited dose-dependent inhibition of inflammatory-related gene expression. A high concentration of S1P (0.5 μM) upregulated osteogenic-related gene expression of OPN, OCN and RUNX2, which also significantly increased the alkaline phosphatase activity, as compared with the control group. In conclusion, S1P coated β-TCP scaffold could inhibit inflammation and promote bone regeneration.