The spinless semi-relativistic Pauli–Fierz Hamiltonian [Formula: see text] in quantum electrodynamics is considered. Here p denotes a momentum operator, A a quantized radiation field, M ≥ 0, Hf the free Hamiltonian of a Boson Fock space and V an external potential. The self-adjointness and essential self-adjointness of H are shown. It is emphasized that it includes the case of M = 0. Furthermore, the self-adjointness and the essential self-adjointness of the semi-relativistic Pauli–Fierz model with a fixed total momentum P ∈ ℝd: [Formula: see text] is also proven for arbitrary P.