In this study, lattice sandwich structures of Ti-6Al-4V alloy with simple cubic (SC) and rhombic dodecahedron (RD) unit cells were prepared by electron beam powder bed fusion (EB-PBF) technique. Through a combination of finite element simulation and experimental investigation, the effect of lattice cell shape and heat treatment on the bending fatigue performance of these lattice sandwich structures was studied. The results show that the underlying fatigue mechanism of the RD lattice sandwich structure is primarily dominated by cyclic ratcheting of the lattice. In contrast, for the SC lattice sandwich structure, the fatigue mechanism involves an interaction of cyclic ratcheting and fatigue crack initiation and propagation of the lattice. During the cyclic deformation process, the struts of the lattice unit cells in the SC lattice sandwich structure mainly undergo buckling deformation. Under the same bending deformation strain, the struts experience much higher stress in the SC lattice sandwich structure, making them more susceptible to crack initiation and resulting in a quick fatigue failure. Therefore, the fatigue performance of the RD lattice sandwich structure is significantly superior to that of the SC lattice sandwich structure. Heat treatment result in the enhanced plasticity of parent materials of the lattice sandwich structure, leading to improved resistance to cyclic strain accumulation during fatigue processes and an increase in fatigue strength.