The Hamiltonian of a system of quantum particles minimally coupled to a quantum field is considered for arbitrary coupling constants. The Hamiltonian has a translation invariant part. By means of functional integral representations the existence of an invariant domain under the action of the heat semigroup generated by a self-adjoint extension of the translation invariant part is shown. With a non-perturbative approach it is proved that the Hamiltonian is essentially self-adjoint on a domain. A typical example is the Pauli–Fierz model with spin 1/2 in nonrelativistic quantum electrodynamics for arbitrary coupling constants.