Lu2Si2O7: Ce (LPS: Ce) is a well-known scintillator due to its excellent scintillation properties such as high light yield and fast decay time. However, the oxygen vacancies would degrade its scintillation properties. In this paper, we perform first-principles investigation on the stabilities of Li, Na, Mg and Ca in LPS and their influences on the oxygen vacancy. We focus on the defect formation energies and densities of states. It is found that the dopants occupy interstitial sites under oxygen-poor limit. They can suppress oxygen vacancies due to the requirement of charge balance. We discuss the influence of dopants on the density of states of perfect LPS.