This work reports the first systematic study of the effects of substitutional doping on the transport properties and electronic structure of CuSbSe. To this end, the electronic structures and thermoelectric parameters of CuSbSe and CuSbM Se (M = Al, Ga, In, Tl, Si, Ge, Sn, Pb, P, As, Bi) were systematically investigated by using density functional theory and the Boltzmann semiclassical transport theory. Substitutional doping at Sb site with IIIA (M = Al, Ga, In, Tl) and IVA (M = Si, Ge, Sn, Pb) elements considerably increases the hole carrier concentration and consequently the electrical conductivity, while doping with M = Bi would be adequate to provide high S values. Changes in calculated thermoelectric parameters are explained based on the effects of the dopant element on the electronic band structure near the Fermi level. We also present an extensive comparison between thermoelectric parameters here calculated and available experimental data. Our results allow us to infer significant insights into the search for new materials with improved thermoelectric performance by modifying the electronic structure through substitutional doping.