The Heusler compound CoTiSb was synthesized and investigated theoretically and experimentally with respect to electronic structure and optical, mechanical, and vibrational properties. The optical properties were investigated in a wide spectral range from 10 meV to 6.5 eV and compared with ab initio calculations. The optical spectra confirm the semiconducting nature of CoTiSb, with a strong exciton absorption at 1.83 eV. The calculated phonon dispersion as well as elastic constants verify the mechanical stability of CoTiSb in the cubic C1 b system. Furthermore, solid solution series of CoTi 1−x M x Sb (M = Sc, V and 0 x 0.2) were synthesized and investigated. The transport properties were calculated by all-electron ab initio methods and compared to the measurements. The thermoelectric properties were investigated by measuring the temperature dependence of electrical resistivity, Seebeck coefficient, and thermal conductivity. The thermal conductivity of the substituted compounds was significantly reduced. Sc substitution resulted in a p-type behavior with a high Seebeck coefficient of + 177.8 μV/K (350 K) at 5% Sc substitution. This value is in good agreement with the calculations. Fully relativistic Korringa-Kohn-Rostoker calculations in combination with the coherent potential approximation clarify the different contribution of states in the (001) plane of the Fermi surface for Sc-or V-substituted compounds CoTi 0.95 M x Sb (M = Sc, V).