La2−xRxCuO4 (R: Pr, Y, Nb) polycrystalline ceramics have been prepared by a spark plasma sintering process. Analysis of the microstructure and phase composition shows that pure La2CuO4 ceramics with a high density can be obtained, and no impurity phases appear. All the samples exhibit a metal–semiconductor transition behavior at ∼750 K, which could be ascribed to the decreasing charge density as a result of loss of oxygen atoms and various conduction mechanisms in these La2CuO4-based ceramics. Our results indicate that the La1.98Y0.02CuO4 ceramics show large thermoelectric power ∼1.0 × 10−3μW·(m·K2)−1, and the evaluated ZT can reach 0.17 at 330 K, which potentially make them useful for thermoelectric applications.