The Seebeck effect in graphene with uniform Kekulé lattice distortion has been studied using the tight-binding model combined with the nonequilibrium Green's function method. The numerical results of this work show that the Seebeck coefficient of the O-shaped Kekulé graphene can be enhanced by modulating the gate voltage. At room temperature (T≈300 K), the Seebeck coefficient for the armchair nanoribbon is Sc≈1370μV/K and for the zigzag nanoribbon is Sc≈1260μV/K. At low temperature (T≈128 K), the Seebeck coefficient for the armchair nanoribbon is Sc≈2500μV/K. In addition, the nano-structuration of the O-shaped Kekulé graphene layer induces an anisotropic behavior in the Seebeck effect. Our work provides an idea for the fabrication of efficient and controllable thermoelectric effect devices.